Inflammatory Signaling Pathway Research Guide: Danger Signal Recognition, Core Signaling Modules, Detection Readouts, and Representative Research Reagents

1. What Is the Inflammatory Response: Defense, Repair, and Dysregulation

The inflammatory response is a protective reaction initiated by the body in response to infection, tissue injury, cellular stress, or disruption of internal homeostasis. Its fundamental purpose is not simply to “produce inflammatory factors,” but to complete three sequential processes: recognizing abnormalities, eliminating threats, and restoring tissue homeostasis.

Acute inflammation is usually protective. Local tissue cells, macrophages, dendritic cells, mast cells, endothelial cells, and other cell types first sense abnormal stimuli. They then release cytokines, chemokines, and lipid mediators, allowing immune cells such as neutrophils and monocytes to enter the inflammatory site and participate in pathogen clearance, removal of necrotic cells, and tissue repair.

However, the inflammatory response must be restricted to an appropriate intensity and duration. If danger stimuli persist, or if negative-feedback and inflammation-resolution mechanisms fail, inflammation can shift from a protective response into a pathological process, leading to tissue damage, fibrosis, immune imbalance, and progression of chronic disease.

Stage of inflammation	Main purpose	Key biological processes	Possible outcome
Initiation	Recognition of infection or tissue injury	PRRs recognize PAMPs/DAMPs; tissue cells and immune cells are activated	Acute inflammation begins
Amplification	Expansion of the local immune response	NF-κB, MAPK, JAK/STAT, IRF, and other pathways are activated; inflammatory gene expression increases	Increased release of inflammatory cytokines and chemokines
Effector phase	Clearance of pathogens, necrotic cells, and injurious factors	Leukocyte recruitment, increased vascular permeability, enhanced phagocytosis, killing, and release of inflammatory mediators	Threats are cleared, or tissue damage is aggravated
Resolution	Termination of inflammation and initiation of repair	Pro-inflammatory signaling declines, apoptotic cells are cleared, and anti-inflammatory factors and pro-resolving mediators increase	Tissue homeostasis is restored, or inflammation progresses to chronicity

2. Where Do Danger Signals Come From: PAMPs, DAMPs, and Cytokines

Inflammation is not an indiscriminately activated response. Cells must first recognize “abnormal signals.” These signals mainly arise from three sources: pathogens, damaged tissues, and immune cells that have already been activated.

2.1 PAMPs: Danger Signals Derived from Pathogens

Pathogen-associated molecular patterns, or PAMPs, are relatively conserved molecular structures found in pathogens and usually absent from host cells. Examples include bacterial lipopolysaccharide, bacterial flagellin, viral double-stranded RNA, viral single-stranded RNA, and unmethylated CpG DNA.

The significance of PAMPs is that they alert the body to the possible presence of infection. They are commonly recognized by pattern recognition receptors, or PRRs, which initiate innate immune responses and further influence adaptive immune responses.

2.2 DAMPs: Danger Signals Derived from Tissue Injury

Damage-associated molecular patterns, or DAMPs, originate from the host’s own cells. Under normal conditions, these molecules are located inside cells or maintained in a controlled state. However, they may be released or exposed during cell necrosis, mechanical injury, ischemia-reperfusion injury, crystal deposition, mitochondrial damage, and other forms of cellular stress.

Common DAMPs include high mobility group box 1, or HMGB1, extracellular ATP, uric acid crystals, mitochondrial DNA, histones, and heat shock proteins. DAMPs help explain why inflammation can occur even in the absence of pathogen infection, such as in trauma, atherosclerosis, gout, and sterile inflammation associated with ischemic tissue injury.

2.3 Cytokines: Secondary Amplification Signals in the Inflammatory Response

Most classical inflammatory cytokines are usually not the initial source of danger signals. Instead, they are secondary amplification signals produced after inflammation has been initiated. Cytokines such as tumor necrosis factor-α, or TNF-α, interleukin-1β, or IL-1β, interleukin-6, or IL-6, and interferons, or IFNs, can act on surrounding cells, expanding the inflammatory response from local recognition to tissue-level or even systemic responses.

Some alarmin-type molecules, such as IL-1α, IL-33, HMGB1, and S100 proteins, may also be released after cellular injury and participate in the initiation of inflammation as DAMP-like signals.

Signal type	Source	Representative molecules	Main significance
PAMPs	Pathogens such as bacteria, viruses, and fungi	LPS, viral RNA, CpG DNA	Indicate infection
DAMPs	Damaged or dying host cells	ATP, HMGB1, uric acid crystals, mitochondrial DNA	Indicate tissue injury or cellular stress
Cytokines	Activated immune cells and tissue cells	TNF-α, IL-1β, IL-6, IFN	Amplify and propagate the inflammatory response

3. Who Recognizes Danger: Receptors and Intracellular Sensors

The inflammatory recognition system can be divided into two layers. The first layer consists of PRRs that directly recognize PAMPs or DAMPs. The second layer consists of receptors that respond to inflammatory cytokines. These two layers serve different functions.

3.1 TLRs: Recognition of Pathogens and Some Damage Signals

Toll-like receptors, or TLRs, are classical PRRs. TLRs are located on the cell membrane or endosomal membrane and can recognize a wide range of microbial components. For example, TLR4 usually forms a complex with MD-2 and recognizes bacterial lipopolysaccharide with the assistance of accessory molecules such as LBP and CD14; TLR3 recognizes double-stranded RNA; TLR7/8 recognizes viral single-stranded RNA; and TLR9 recognizes CpG DNA.

After TLR activation, signals are transmitted through myeloid differentiation primary response 88, or MyD88, or TIR-domain-containing adapter-inducing interferon-β, or TRIF. This activates nuclear factor kappa-light-chain-enhancer of activated B cells, or NF-κB, mitogen-activated protein kinase, or MAPK, and interferon regulatory factor, or IRF.

3.2 TNFR, IL-1R, IL-6R, and IFNAR: Receptors That Respond to Inflammatory Cytokines

Tumor necrosis factor receptor, or TNFR, interleukin-1 receptor, or IL-1R, interleukin-6 receptor, or IL-6R, and type I interferon receptor, or IFNAR, generally do not directly recognize pathogens. Instead, they respond to inflammatory cytokines that have already been produced.

TNFR and IL-1R mainly connect to the NF-κB and MAPK pathways, promoting inflammatory cytokine expression, endothelial cell activation, and amplification of inflammation. IL-6R and IFNAR mainly connect to the Janus kinase/signal transducer and activator of transcription pathway, or JAK/STAT, and participate respectively in acute-phase responses, immune-cell differentiation, and antiviral gene expression.

3.3 NLRP3: Sensing Intracellular Stress and Promoting IL-1β Maturation

NLR family pyrin domain containing 3, or NLRP3, is an intracellular danger-sensing molecule. It does not correspond simply to a single ligand. Instead, it responds to multiple cellular stress events, such as potassium efflux, lysosomal damage, mitochondrial dysfunction, changes in reactive oxygen species, or ROS, and crystal stimulation.

After activation, NLRP3 forms an inflammasome complex with apoptosis-associated speck-like protein containing a CARD, or ASC, and pro-caspase-1. Activated caspase-1 then cleaves pro-IL-1β and pro-IL-18 into mature IL-1β and IL-18, and can mediate pyroptosis through gasdermin D, or GSDMD.

3.4 cGAS-STING: Recognition of Cytosolic DNA and Induction of Type I Interferons

Cyclic GMP-AMP synthase, or cGAS, can recognize double-stranded DNA that abnormally appears in the cytosol. After being activated by DNA, cGAS catalyzes ATP and GTP to generate 2′3′-cyclic GMP-AMP, or 2′3′-cGAMP. 2′3′-cGAMP then binds to stimulator of interferon genes, or STING, further activating the TBK1–IRF3 axis and inducing IFN-β and interferon-stimulated gene expression. At the same time, STING can also activate NF-κB-related inflammatory gene expression.

Cytosolic dsDNA

↓

cGAS activation

↓

ATP + GTP → 2′3′-cGAMP + PPi

↓

STING → TBK1 → IRF3 / NF-κB

↓

IFN-β, interferon-stimulated genes, and inflammatory cytokine expression

4. Four Core Inflammatory Axes: NF-κB, MAPK, JAK/STAT, and Inflammasomes/IRF

The complexity of inflammatory signaling pathways mainly arises from the fact that different upstream signals converge on a limited number of core pathways. To understand inflammation, it is essential to understand what biological question each of these core pathways addresses.

Core pathway/module	Major upstream stimuli	Key molecular events	Major outputs
NF-κB	TLRs, TNFR, IL-1R	IκBα degradation; p65/p50 nuclear translocation	TNF-α, IL-6, IL1B, chemokines, COX-2
MAPK	TLRs, TNFR, IL-1R, stress stimuli	Phosphorylation of p38, JNK, and ERK	AP-1 activation, inflammatory gene expression, regulation of mRNA stability
JAK/STAT	IL-6, IFN, GM-CSF, IL-10, etc.	STAT phosphorylation, dimerization, and nuclear translocation	Acute-phase responses, antiviral genes, immune-cell differentiation
IRF	TLR3, TLR7/8, TLR9, RIG-I-like receptors, cGAS-STING	Activation and nuclear translocation of IRF3/7	Type I interferons, ISGs
Inflammasome	NLRP3 activation, ATP, crystals, K⁺ efflux, mitochondrial damage, etc.	ASC speck formation, caspase-1 activation, GSDMD cleavage	Mature IL-1β/IL-18 release, pyroptosis

4.1 NF-κB: A Key Pathway for Inflammatory Gene Transcription

NF-κB is one of the central transcriptional regulatory pathways in the inflammatory response. Under resting conditions, the classical NF-κB dimer p65/p50 is retained in the cytoplasm by the inhibitory protein IκBα. After activation of TLRs, TNFR, or IL-1R, the IκB kinase complex, or IKK, phosphorylates IκBα, leading to its ubiquitination and proteasomal degradation. p65/p50 then enters the nucleus and induces the expression of inflammation-related genes.

TLR / TNFR / IL-1R → TAK1 / IKK complex → IκBα phosphorylation and degradation → NF-κB p65/p50 nuclear translocation → transcription of genes such as TNF, IL6, IL1B, CCL2, CXCL8, and PTGS2

The importance of NF-κB lies in the fact that it controls a group of inflammatory genes rather than a single molecule. TNF-α, IL-6, the IL-1β precursor, chemokines, and cyclooxygenase-2, or COX-2, also known as PTGS2, may all be regulated by NF-κB. Therefore, p-p65, IκBα degradation, and p65 nuclear translocation are commonly used indicators for evaluating NF-κB activation.

4.2 MAPK: A Pathway for Inflammatory Signal Amplification and Stress Responses

The MAPK pathway includes branches such as p38, c-Jun N-terminal kinase, or JNK, and extracellular signal-regulated kinase, or ERK. TLRs, TNFR, IL-1R, and multiple cellular stress stimuli can all activate MAPK signaling.

The main function of MAPK is to enhance inflammatory gene expression. On one hand, it activates transcription factors such as activator protein 1, or AP-1. On the other hand, it affects the stability and translational efficiency of inflammation-related mRNAs through downstream kinases. p38 and JNK are often closely associated with stress responses and the production of TNF-α, IL-6, and chemokines; ERK participates in immune-cell activation, proliferation, and certain inflammatory responses.

TLR / TNFR / IL-1R / cellular stress

↓

MAP3K → MAP2K

↓

p38 / JNK / ERK

↓

AP-1 activation and altered mRNA stability

↓

Enhanced expression of inflammatory cytokines and chemokines

4.3 JAK/STAT: A Cytokine-Driven Pathway for Inflammatory Propagation

The JAK/STAT pathway is mainly responsible for cytokine signal transduction. After cytokines such as IL-6, IFN, granulocyte-macrophage colony-stimulating factor, or GM-CSF, and IL-10 bind to their receptors, they activate JAK family kinases, which then phosphorylate STAT proteins. STAT proteins dimerize and enter the nucleus to regulate target gene expression.

Different STAT proteins correspond to different functions. STAT1 and STAT2 mainly participate in IFN-mediated antiviral responses. STAT3 can be activated by IL-6, IL-10, and other cytokines, and plays roles in acute-phase responses, T-cell differentiation, macrophage function, and inflammatory regulation. STAT5 is associated with signaling by multiple hematopoietic and immune-cell cytokines.

The JAK/STAT pathway should not be understood simply as a “pro-inflammatory pathway.” The same STAT3 can promote inflammation and acute-phase responses in IL-6 signaling, while mediating anti-inflammatory effects in IL-10 signaling. Therefore, when interpreting JAK/STAT experimental results, the upstream cytokine, cell type, and downstream target genes must all be considered.

4.4 Inflammasomes and IRF: Determining IL-1β Maturation and Antiviral Responses

The production of IL-1β differs from that of TNF-α and IL-6. TNF-α and IL-6 mainly depend on transcriptional and secretory regulation, whereas IL-1β usually requires “two-step activation.”

The first step is the priming signal. Activation of NF-κB by TLRs, TNFR, or IL-1R induces the expression of NLRP3 and pro-IL-1β. The second step is the activation signal. Stimuli such as ATP, crystals, potassium efflux, and mitochondrial damage induce assembly of the NLRP3 inflammasome, activate caspase-1, and cleave pro-IL-1β, pro-IL-18, and GSDMD, thereby promoting mature IL-1β/IL-18 release and pyroptosis.

Signal 1: Priming

TLR / TNFR / IL-1R → NF-κB → Increased expression of NLRP3 and pro-IL-1β

Signal 2: Activation

K+ efflux / ATP / crystals / mitochondrial damage

↓

Assembly of the NLRP3-ASC-pro-caspase-1 complex

↓

Caspase-1 activation

↓

pro-IL-1β → IL-1β

pro-IL-18 → IL-18

GSDMD → GSDMD-N → Membrane pore formation and pyroptosis

The IRF pathway is mainly associated with nucleic acid recognition and antiviral responses. TLR3, TLR7/8, TLR9, RIG-I-like receptors, and the cGAS-STING pathway can all activate IRF3 or IRF7, inducing the expression of type I interferons and interferon-stimulated genes, or ISGs. The IRF pathway enables the body to establish an antiviral state during the inflammatory response, rather than merely producing classical pro-inflammatory cytokines.

5. Inflammatory Outputs: Cytokines, Chemokines, and Lipid Mediators

The ultimate significance of inflammatory pathways lies in their functional outputs. To determine whether inflammation has truly occurred, it is not sufficient to examine only upstream pathway phosphorylation. It is also necessary to assess whether downstream inflammatory molecules are expressed and secreted, and whether they induce changes in cellular behavior.

5.1 Major Inflammatory Cytokines

TNF-α is an early pro-inflammatory cytokine. It can activate endothelial cells and promote adhesion molecule expression, making it easier for leukocytes to enter inflammatory sites. TNF-α can also further activate NF-κB and MAPK, forming an inflammatory amplification loop.

IL-1β is a potent pro-inflammatory cytokine involved in fever, endothelial activation, neutrophil recruitment, and local tissue inflammation. Its key feature is that it requires inflammasome-mediated maturation; therefore, mature IL-1β reflects inflammasome activity more directly than IL1B mRNA.

IL-6 is an important cytokine linking local inflammation to systemic responses. Through the IL-6R/gp130-JAK/STAT3 pathway, IL-6 participates in acute-phase protein expression, B-cell function, T-cell differentiation, and the regulation of chronic inflammation.

Type I interferons mainly include IFN-α and IFN-β. They are responsible for inducing antiviral gene expression and shifting cells into an antiviral state.

5.2 Chemokines Determine Immune-Cell Recruitment

The main function of chemokines is to guide immune-cell migration. CXCL8/IL-8 is commonly associated with neutrophil recruitment, CCL2 with monocyte recruitment, and CXCL10 with T cells, natural killer cells, and antiviral inflammatory responses. If cytokines are responsible for “enhancing the inflammatory response,” then chemokines are responsible for “determining which cells arrive at the inflammatory site.”

5.3 COX-2 and Prostaglandins Participate in Fever, Pain, and Vascular Responses

COX-2 is an important enzyme for lipid mediator synthesis during inflammation. Membrane phospholipids release arachidonic acid through phospholipase A2. Arachidonic acid is then converted by COX-2 into prostaglandin H2, which further generates lipid mediators such as PGE2, PGI2, and TXA2. These mediators participate respectively in fever, pain, vascular tone regulation, platelet responses, and local inflammatory regulation.

Membrane phospholipids

↓ Phospholipase A2

Arachidonic acid

↓ COX-2 / PTGS2

PGG2 → PGH2

↓

Prostaglandin-type mediators such as PGE2, PGI2, and TXA2

↓

Fever, pain, vascular tone regulation, platelet responses, and inflammatory regulation

Output type	Representative molecules	Main functions	Common detection methods
Pro-inflammatory cytokines	TNF-α, IL-1β, IL-6	Inflammatory amplification, tissue responses, immune-cell activation	ELISA, qPCR, Western blot, flow cytometry
Antiviral factors	IFN-α, IFN-β, ISGs	Establishment of an antiviral state	qPCR, ELISA, RNA-seq
Chemokines	CXCL8, CCL2, CXCL10	Recruitment of neutrophils, monocytes, and T cells	qPCR, ELISA, Luminex
Lipid mediators	PGE2, PGI2, TXA2	Fever, pain, vascular tone regulation, platelet responses	LC-MS, ELISA
Cell-death-related molecules	Cleaved caspase-1, GSDMD-N	Pyroptosis and IL-1β release	Western blot, immunofluorescence, flow cytometry

6. How Inflammation Is Turned Off: Negative Feedback, Anti-Inflammatory Signaling, and Resolution

The inflammatory response must be shut down. Otherwise, persistent release of pro-inflammatory factors, continuous immune-cell infiltration, and ongoing tissue-cell damage can drive chronic inflammation and fibrosis.

6.1 Pathway-Intrinsic Negative Feedback

After NF-κB activation, not only pro-inflammatory genes but also inhibitory factors are induced. For example, newly synthesized IκBα can bind NF-κB again and retain it in the cytoplasm. A20/TNFAIP3 can inhibit ubiquitination signals downstream of TNFR, TLRs, and IL-1R, thereby limiting sustained NF-κB activation.

The MAPK pathway also contains negative-feedback mechanisms. Dual-specificity phosphatases, or DUSPs, can dephosphorylate MAPKs and reduce the activity of p38, JNK, or ERK.

The major negative regulators of the JAK/STAT pathway are the suppressor of cytokine signaling, or SOCS, family proteins. SOCS proteins can inhibit JAK activity or promote degradation of signaling complexes, thereby limiting sustained cytokine signal transduction.

6.2 Anti-Inflammatory Cytokines

IL-10 is an important anti-inflammatory cytokine that can inhibit macrophages and dendritic cells from producing pro-inflammatory factors such as TNF-α, IL-1β, and IL-6. Transforming growth factor-β, or TGF-β, participates in immune suppression, tissue repair, and regulation of fibrosis. Anti-inflammatory cytokines do not simply “reduce inflammation”; rather, they help the inflammatory response transition from the clearance phase to the repair phase.

6.3 Resolution of Inflammation Is an Active Process

Resolution of inflammation is not merely the natural depletion of pro-inflammatory factors. It is an active process jointly completed through cell clearance, lipid mediator switching, and tissue repair. The process by which macrophages engulf apoptotic neutrophils is called efferocytosis. Efferocytosis helps reduce leakage of cellular contents and promotes anti-inflammatory and reparative signaling.

Specialized pro-resolving mediators, or SPMs, include lipoxins, resolvins, protectins, and maresins. These mediators can limit neutrophil infiltration, promote clearance of dead cells, and drive tissues back toward homeostasis.

Acute inflammation → Clearance of pathogens or injurious substances → Neutrophil apoptosis → Macrophage efferocytosis → Increased IL-10, TGF-β, and SPMs → Inflammation resolution and tissue repair

7. What Indicators Should Be Examined When Studying Inflammatory Pathways?

Reliable experimental design for inflammation research should cover the full chain of “upstream stimulus—signal activation—gene transcription—protein secretion—cellular function.”

Research level	Question to answer	Common indicators	Common methods
Upstream stimulus	What initiates inflammation?	LPS, ATP, HMGB1, mtDNA, TNF-α, IL-1β, IL-6	Stimulation models, ELISA, qPCR, immunodetection
NF-κB	Has inflammatory gene transcription been initiated?	p-p65, IκBα degradation, p65 nuclear translocation	Western blot, immunofluorescence, nuclear-cytoplasmic fractionation
MAPK	Has stress response and inflammatory amplification occurred?	p-p38, p-JNK, p-ERK	Western blot, phospho-flow cytometry
JAK/STAT	Is cytokine signaling being transduced?	p-STAT1, p-STAT3, p-STAT5	Western blot, flow cytometry, immunofluorescence
IRF/cGAS-STING	Is an antiviral or cytosolic DNA response activated?	cGAS, STING, p-TBK1, p-IRF3, IFNB1, ISGs	Western blot, qPCR, RNA-seq
Inflammasome	Has IL-1β matured and been released?	NLRP3, ASC speck, cleaved caspase-1, GSDMD-N, mature IL-1β	Western blot, ELISA, immunofluorescence
Inflammatory output	Has a functional inflammatory response been produced?	TNF-α, IL-6, IL-1β, CCL2, CXCL8, PGE2	ELISA, Luminex, LC-MS, qPCR
Cellular function	Does inflammation alter cellular behavior?	Migration, phagocytosis, pyroptosis, cell death, tissue infiltration	Transwell assay, flow cytometry, tissue staining, live-cell imaging

7.1 Time Points Determine the Interpretation of Results

Inflammatory signaling has a clear temporal sequence. Phosphorylation of NF-κB, MAPK, and JAK/STAT usually appears within minutes to 1 hour after stimulation. Inflammatory gene transcription often increases within several hours. Cytokine protein secretion and cell migration usually occur later. Therefore, inflammation experiments should distinguish at least three temporal levels:

Temporal level	Main observation target	Representative indicators
Early signaling	Pathway phosphorylation and transcription factor nuclear translocation	p-p65, p-p38, p-STAT3, p-IRF3
Intermediate transcription	Inflammatory gene expression	TNF, IL6, IL1B, CXCL8, CCL2, PTGS2
Late effector phase	Protein secretion and cellular function	TNF-α, IL-6, IL-1β, PGE2, cell migration, pyroptosis

7.2 Inhibitor-Based Results Require Causal Validation

Inflammatory pathways are subject to extensive crosstalk. NF-κB, MAPK, JAK/STAT, IRF, and inflammasomes are not isolated linear pathways. Small-molecule inhibitors can indicate that a pathway is involved, but because they may have off-target effects, more reliable conclusions require a combination of gene knockdown, knockout, overexpression, rescue experiments, and multi-indicator detection.

For example, to demonstrate that a treatment inhibits the NLRP3 inflammasome, it is not sufficient to detect only a decrease in IL-1β. NLRP3 expression, ASC speck formation, cleaved caspase-1, GSDMD-N, and mature IL-1β should also be examined, and artifacts caused by cell death or global transcriptional suppression should be excluded.

8. Summary: Inflammatory Pathways Are a Continuous Process of “Recognition—Amplification—Output—Braking”

Immunoinflammatory signaling pathways consist of multiple recognition systems and downstream signaling modules that form a continuous response.

1. Recognition: TLRs, NLRP3, cGAS-STING, and other sensors recognize PAMPs, DAMPs, or abnormal cytosolic nucleic acids; TNFR, IL-1R, IL-6R, IFNAR, and other receptors respond to inflammatory cytokines.

2. Amplification: NF-κB, MAPK, JAK/STAT, and IRF convert upstream stimuli into changes in gene expression.

3. Output: TNF-α, IL-1β, IL-6, IFNs, chemokines, and COX-2-related lipid mediators jointly drive immune-cell recruitment, local tissue responses, and systemic inflammatory responses.

4. Braking: IκBα, A20, DUSPs, SOCS, IL-10, TGF-β, efferocytosis, and SPMs limit sustained inflammatory activation and promote inflammation resolution and tissue repair.

The key to understanding inflammatory pathways is to address four questions:

Where do danger signals come from?

Which receptors or sensors recognize them?

Through which core pathways are they amplified?

What inflammatory outputs are ultimately produced, and how is the response shut down?

Only by answering these four questions together can we truly understand the role of immunoinflammatory signaling pathways in host defense against infection, tissue injury, chronic inflammation, and disease development.

The core logic of immunoinflammatory signaling pathways is shown in the figure below:

 

9. Classification Table of Representative Chemicals Related to Immunoinflammatory Signaling Pathways

Table 1. Stimuli for Danger Signal Recognition and Inflammatory Models

Category	CAS No.	Aladdin Cat. No.	Name	Specification or Purity	Product Features and Applications
Toll-like receptor 4 stimulant	93572-42-0	L386714	Lipopolysaccharide (LPS)	From Escherichia coli 055:B5, purified by trichloroacetic acid extraction	Used to establish inflammation models induced by bacterial components and to study Toll-like receptor 4-mediated activation of NF-κB and MAPK, as well as the expression of inflammatory genes such as TNF-α, IL-6, and IL1B.
Toll-like receptor 1/2 lipopeptide agonist	112208-00-1	rp174719	Pam3CSK4	Moligand™	Used to study the Toll-like receptor 1/2–MyD88 pathway; suitable for experiments on NF-κB and MAPK phosphorylation and pro-inflammatory cytokine release.
Toll-like receptor 2/6 lipopeptide agonist	322455-70-9 (free base)	F276522	FSL-1 TFA	≥98%	Used for research on Toll-like receptor 2/6-related inflammatory signaling; suitable for detecting NF-κB and MAPK activation, as well as indicators such as TNF-α and IL-6.
Viral double-stranded RNA mimic	24939-03-5	P588406	Polyinosinic-polycytidylic acid, Poly(I:C)	Moligand™, ≥90%	Used to mimic viral double-stranded RNA stimulation and to study Toll-like receptor 3- and MDA5-related IRF and NF-κB activation, as well as type I interferon responses.
Toll-like receptor 7 agonist	99011-02-6	I129798	Imiquimod	Moligand™, ≥98%	Used for research on Toll-like receptor 7-related immune activation; suitable for antiviral immunity, skin inflammation, and cytokine-induction models.
Toll-like receptor 7/8 agonist	144875-48-9	R131891	Resiquimod	Moligand™, ≥98% (HPLC)	Used for innate immune research related to nucleic acid sensing; can induce Toll-like receptor 7/8-mediated activation of NF-κB and IRF pathways and inflammatory cytokine expression.
Toll-like receptor 9 oligonucleotide agonist	202668-42-6	O648633	ODN 1826	≥98%	Used for innate immune research related to CpG DNA; suitable for detecting mouse Toll-like receptor 9-mediated immune-cell activation and inflammatory cytokine expression.
Urate crystal stimulant	1198-77-2	U166391	Uric acid sodium salt	Na 11–13%	Used for research on urate crystal-associated sterile inflammation. In experiments, MSU crystals usually need to be prepared and validated according to the protocol, with control of crystal size, sterility, and endotoxin contamination. Suitable for gout-like inflammation, NLRP3 inflammasome activation, and IL-1β maturation and release experiments.
Particulate adjuvant / sterile inflammation stimulant	21645-51-2	A110527	Aluminum hydroxide	PrimorTrace™, ≥99.99% metals basis, 2–10 μm	Used for research on aluminum hydroxide adjuvant-related immune activation; suitable for detecting phagocyte responses, inflammasome-related indicators, and cytokine release. The relationship between its in vivo adjuvant effect and NLRP3 is model-dependent and should be interpreted according to the specific experimental system.
Second signal for NLRP3 inflammasome activation	987-65-5	A100880	Adenosine 5′-triphosphate disodium salt (ATP)	≥98%	Used in NLRP3 inflammasome activation experiments after LPS priming; induces P2X7-related potassium efflux, caspase-1 activation, and mature IL-1β release.
NLRP3 inflammasome activator	28643-80-3	N102401	Nigericin sodium	≥98%	Used to induce potassium efflux and NLRP3 inflammasome activation; suitable for detecting caspase-1, GSDMD, and mature IL-1β.

Table 2. Products Related to the NF-κB/IKK Pathway and Inflammatory Transcriptional Regulation

Category	CAS No.	Aladdin Cat. No.	Name	Specification or Purity	Product Features and Applications
IκBα/NF-κB and NLRP3 inflammasome-related inhibitor	19542-67-7	B129693	BAY 11-7082, IκBα kinase inhibitor	Moligand™, ≥98%	Used to study IκBα phosphorylation, NF-κB activation, and inflammatory gene transcriptional regulation; it may also affect NLRP3 inflammasome activation. Suitable for detecting indicators such as TNF-α, IL-6, COX-2, and IL-1β. Multi-target effects should be considered when interpreting mechanisms.
IKKβ/NF-κB pathway inhibitor	507475-17-4	T126861	TPCA-1, IκB kinase inhibitor	Moligand™, ≥98%	Used for mechanistic validation of the IKKβ–NF-κB axis; suitable for evaluating p65 activation, inflammatory cytokine expression, and chemokine release after inflammatory stimulation.
IKK complex inhibitor	873225-46-8	I129698	IKK-16 (IKK Inhibitor VII)	≥99%	Used to block IKK complex-related signaling and to study NF-κB activation and downstream pro-inflammatory gene expression after inflammatory stimulation.
IKKβ/NF-κB pathway inhibitor	354812-17-2	S126740	SC-514, reversible ATP-competitive IKKβ/IKK-2 inhibitor	≥98%	Used for studies of IKKβ-dependent NF-κB signaling; suitable for experiments on the regulation of inflammatory cytokines, chemokines, and COX-2 expression.
NF-κB p65 nuclear translocation inhibitor	749886-87-1	M134534	4-Methyl-N1-(3-phenylpropyl)benzene-1,2-diamine	≥98% (HPLC)	Used to study NF-κB p65 nuclear translocation and transcriptional activity; suitable for immunofluorescence, nuclear-cytoplasmic fractionation, and inflammatory cytokine expression experiments.
Proteasome/IκB degradation modulator	133407-82-6	M126521	MG-132, reversible proteasome inhibitor	Moligand™, ≥98%	Used to study proteasome-mediated IκB degradation, NF-κB signaling regulation, and changes in the stability of inflammation-related proteins.
Natural product inflammation modulator	20554-84-1	P115736	Parthenolide	Analytical standard, Moligand™, ≥98%	Used for research related to NF-κB, inflammasomes, and pro-inflammatory cytokine expression; suitable for evaluating the anti-inflammatory activity of natural products and for inflammatory signaling intervention experiments.

Table 3. Products Related to the MAPK Pathway

Category	CAS No.	Aladdin Cat. No.	Name	Specification or Purity	Product Features and Applications
p38 MAPK inhibitor	152121-30-7	S134307	SB 202190, p38 MAPK inhibitor	Moligand™, ≥99%	Used for p38 MAPK pathway research; suitable for detecting inflammatory cytokine expression, stress responses, and mechanisms of pro-inflammatory signal amplification.
p38 MAPK inhibitor	152121-47-6	S131899	SB-203580, p38 MAPK inhibitor	Moligand™, ≥98% (HPLC)	Used for validation of the p38 MAPK branch; suitable for studies on TNF-α, IL-6, chemokines, and inflammation-related mRNA stability.
p38 MAPK inhibitor	285983-48-4	D125100	Doramapimod	Moligand™, ≥99%	Used for research on p38 MAPK-related inflammatory signaling; suitable for cytokine production, stress responses, and inflammatory pathway intervention experiments.
JNK pathway inhibitor	129-56-6	S125267	Anthra[1,9-cd]pyrazol-6(2H)-one	Moligand™, ≥98%	Used for research on JNK-related inflammatory signaling; suitable for studies of the c-Jun/AP-1 pathway and regulation of pro-inflammatory cytokine expression.
JNK pathway inhibitor	1410880-22-6	J125321	JNK-IN-8	Moligand™, ≥98%	Used for JNK signaling research; suitable for mechanistic validation of c-Jun phosphorylation, AP-1 activation, and stress-related inflammatory responses.
MEK/ERK pathway inhibitor	167869-21-8	P126620	2-(2-Amino-3-methoxyphenyl)chromone	Moligand™, ≥98%	Used for MEK/ERK pathway research; suitable for detecting ERK phosphorylation, AP-1-related transcription, and inflammatory cytokine expression after inflammatory stimulation.
MEK/ERK pathway inhibitor	109511-58-2	U274745	U0126, MKK inhibitor	Moligand™, ≥98%	Used to block MEK1/2–ERK signaling; suitable for analyzing the involvement and downstream effects of the ERK pathway after inflammatory stimulation.
ERK pathway inhibitor	942183-80-4	S127539	SCH772984	Moligand™, ≥98%	Used for research on ERK1/2-related inflammation and cell activation; suitable for detecting ERK phosphorylation, inflammatory gene expression, and changes in cellular responses.

Table 4. Products Related to JAK/STAT Cytokine Signaling

Category	CAS No.	Aladdin Cat. No.	Name	Specification or Purity	Product Features and Applications
JAK pathway inhibitor	540737-29-9	E129454	Tofacitinib citrate (CP-690550)	Moligand™, ≥99%	Used for research on JAK-dependent cytokine signaling; suitable for analyzing STAT phosphorylation and downstream gene expression after inflammatory cytokine stimulation.
JAK1 pathway inhibitor	1310726-60-3	U302354	Upadacitinib (ABT-494)	Moligand™, ≥99%	Used for research on JAK1-related cytokine signaling; suitable for detecting STAT phosphorylation and target gene expression in inflammatory pathways involving IL-6, interferons, and other mediators.
JAK1/2 pathway inhibitor	1187594-09-7	B127687	Baricitinib	Moligand™, ≥99%	Used for research on JAK1/2-mediated inflammatory cytokine signaling; suitable for experiments on STAT activation, acute-phase responses, and immune-cell functional regulation.
JAK1/2 pathway inhibitor	941678-49-5	R126338	Ruxolitinib (INCB018424)	Moligand™, ≥98%	Used for research on JAK1/2-mediated IL-6, interferon, and other cytokine signaling; suitable for detecting STAT phosphorylation and interferon-stimulated gene expression.
JAK2 pathway inhibitor	936091-26-8	T126330	Fedratinib (SAR302503, TG101348)	Moligand™, ≥98%	Used for research on JAK2-related signaling; suitable for analyzing cytokine-induced STAT activation, inflammatory responses, and immune-cell function.
JAK2-related tyrosine kinase inhibitor	133550-30-8	A126525	Tyrosine Kinase Inhibitor AG 490	Moligand™, ≥98%	Used for research on JAK2/STAT-related inflammatory signaling; can be used to detect STAT phosphorylation and pro-inflammatory gene expression after cytokine stimulation.
STAT3 pathway inhibitor	19983-44-9	S129623	6-Nitrobenzo[b]thiophene-1,1-dioxide	Moligand™, ≥98%	Used for research on STAT3 activation and transcriptional regulation; suitable for detecting IL-6/STAT3-related inflammatory signaling and target gene expression.
STAT3 pathway inhibitor	501919-59-1	S129625	S3I-201, STAT3 inhibitor	≥96%	Used for research on STAT3 dimerization and transcriptional activity; suitable for analysis of the IL-6/STAT3 axis and inflammation-related target gene expression.

Table 5. Products Related to the NLRP3 Inflammasome, Caspase-1, and Pyroptosis

Category	CAS No.	Aladdin Cat. No.	Name	Specification or Purity	Product Features and Applications
Microtubule/NLRP3-related inflammation modulator	64-86-8	C106738	Colchicine	Moligand™, ≥98%	Used for research on gout-like inflammation, microtubule-related immune regulation, and NLRP3 inflammasome-related responses.
NLRP3 inflammasome-related inhibitor	10238-21-8	G127198	Glibenclamide	Moligand™, ≥99%	Used for research on the NLRP3 inflammasome; suitable for experiments on mature IL-1β release, caspase-1 activation, and regulation of inflammatory responses.
NLRP3 inflammasome inhibitor	1073612-91-5	C288007	CY-09, NLRP3 inhibitor	Moligand™, ≥98% (HPLC)	Used for research on the mechanism of NLRP3 activation; can be used to validate NLRP3-dependent IL-1β release and inflammasome assembly-related processes.
NLRP3 inflammasome inhibitor	54863-37-5	D286906	Dapansutrile (OLT1177, 3-(methylsulfonyl)propanenitrile)	Moligand™, ≥98%	Used for intervention experiments targeting the NLRP3 inflammasome pathway; suitable for detecting caspase-1 activation, IL-1β maturation, and inflammatory outputs.
NLRP3 inflammasome inhibitor	210826-40-7	M414276	MCC950	Moligand™, ≥97%	Used for research on NLRP3-dependent inflammasome responses; suitable for detecting ASC speck formation, caspase-1 activation, and IL-1β release.
Caspase-1 inhibitor	273404-37-8	B275738	Belnacasan (VX-765)	Moligand™, ≥98%	Used for research on caspase-1-mediated maturation of IL-1β and IL-18; suitable for inflammasome functional validation and pyroptosis-related detection.
Caspase-1 inhibitor	178603-78-6	C343789	Caspase-1 Inhibitor II	≥95%	Used for caspase-1 activity inhibition experiments; suitable for validating IL-1β maturation, IL-18 release, and NLRP3 inflammasome function.
Pan-caspase inhibitor	187389-52-2	V275259	Z-VAD(OMe)-FMK, cell-permeable irreversible pan-caspase inhibitor	Moligand™, ≥98%	Used for research on caspase-dependent cell death; suitable for distinguishing apoptosis, pyroptosis, and inflammasome-related cell death processes.
GSDMD/pyroptosis modulator	97-77-8	T110101	Tetraethylthiuram disulfide (TETD; disulfiram)	Moligand™, ≥97%	Used for research on GSDMD-related pyroptosis; suitable for analyzing inflammasome downstream membrane pore formation, IL-1β release, and cell death.
GSDMD/MLKL-related cell death inhibitor	1360614-48-7	N302487	Necrosulfonamide, necroptosis inhibitor	≥99%	Used for research on programmed cell death mechanisms; suitable for distinguishing necroptosis, pyroptosis, and inflammasome-related cell death pathways.

Table 6. Products Related to cGAS-STING/TBK1-IRF, COX Lipid Mediators, and Inflammation Resolution

Category	CAS No.	Aladdin Cat. No.	Name	Specification or Purity	Product Features and Applications
Endogenous STING second messenger	1441190-66-4	C1434818	2′,3′-cGAMP	≥99%	Used for STING pathway activation research; suitable for detecting TBK1-IRF3 phosphorylation, type I interferon production, and interferon-stimulated gene expression.
STING pathway agonist	2138299-34-8	D647671	diABZI STING agonist-1 trihydrochloride	Moligand™, ≥98%	Used for STING–TBK1–IRF3 pathway activation research; suitable for detecting type I interferons, interferon-stimulated genes, and inflammatory cytokine expression.
Mouse STING pathway agonist	117570-53-3	D129922	DMXAA (Vadimezan), vascular disrupting agent	Moligand™, ≥98%	Used for research on mouse STING-related signaling; can induce TBK1-IRF3 activation and type I interferon responses. Suitable for mouse-derived cells and model experiments; not recommended for human STING activation models.
STING pathway antagonist	941987-60-6	H287635	H-151, STING antagonist	Moligand™, ≥98% (HPLC)	Used for research on STING-mediated inflammation and type I interferon responses; suitable for validation of the cytosolic DNA–STING–TBK1–IRF3 pathway.
STING pathway inhibitor	314054-00-7	C288157	C-176, STING inhibitor	≥97% (HPLC)	Used for research on STING-related inflammatory signaling; commonly used for validation of mouse STING pathway activation, TBK1-IRF3 activation, and type I interferon responses.
cGAS pathway inhibitor	2262452-06-0	R413655	RU.521	≥99%	Used for research on cGAS-dependent cytosolic DNA sensing; suitable for validating the role of cGAS in STING activation and type I interferon responses.
cGAS pathway inhibitor	2369751-30-2	G414285	G150	≥98%	Used for research on cGAS-related signaling; suitable for analyzing cytosolic DNA-induced STING activation, IRF3 phosphorylation, and inflammatory gene expression.
TBK1/IKKε/PDK1-related multi-kinase inhibitor	702675-74-9	B126947	BX-795, PDK1 inhibitor	Moligand™, ≥97%	Used for research on TBK1/IKKε–IRF3-related signaling; suitable for analyzing type I interferon responses and cytosolic nucleic acid sensing pathways.
Lipid inflammatory mediator precursor	506-32-1	A131025	Arachidonic acid (AA)	Moligand™, ≥99% (GC)	Used for research on lipid inflammatory mediators such as prostaglandins and leukotrienes; suitable for studies of COX and LOX pathways and inflammatory outputs.
Prostaglandin-type inflammatory mediator	363-24-6	D133402	Dinoprostone	Moligand™, ≥98%	Used for research on PGE2-related inflammatory effects; suitable for studies of fever, pain, vascular responses, and regulation of immune-cell function.
COX-2 pathway inhibitor	169590-42-5	C129279	Celecoxib	Moligand™, ≥99%	Used for COX-2/PGE2 pathway research; suitable for detecting inflammatory lipid mediators, pain-associated inflammatory responses, and prostaglandin generation.
COX-2 pathway inhibitor	123653-11-2	N274713	NS 398, COX-2 inhibitor	Moligand™, ≥98%	Used for research on COX-2-mediated prostaglandin synthesis; suitable for detecting PGE2 production, inflammatory lipid mediators, and pro-inflammatory responses.
Lipid mediator of inflammation resolution	872993-05-0	R341442	Resolvin D1	Moligand™, ≥95%, a solution in ethanol	Used for inflammation-resolution research; suitable for studies of macrophage efferocytosis, reduction of inflammatory cytokines, and tissue repair-related experiments.
Broad-spectrum anti-inflammatory positive control	50-02-2	D137736	Dexamethasone	≥98%	Used as an anti-inflammatory positive control and for glucocorticoid-response research; suitable for evaluating inflammatory cytokine expression, immune-cell activation, and anti-inflammatory effects.

Note: The compounds listed above are mainly used for pathway stimulation, inhibition, or mechanistic validation in scientific research experiments. Because small-molecule inhibitors may show concentration-dependent effects, cell type-specific differences, and off-target effects, experimental conclusions should be evaluated comprehensively by combining dose gradients, time points, cell viability assays, multiple readouts, and genetic validation. Relevant products are for research use only and are not intended for human diagnosis or treatment. For additional product specifications, grades, and COA information, please search by “product name/CAS/catalog number” on the Aladdin website.

For more related articles, see below:

Regulatory Framework and Biological Effects of the GSK3 Signaling Pathway

BMP Signaling Pathway: Molecular Components, Signal Transduction Mechanisms, and Biological Functions

RANK Signaling Pathway: Molecular Components, Activation Mechanisms, and Biological Effects

CTLA4 Signaling Pathway: Molecular Basis, Immunoregulatory Mechanisms, and Disease Associations

Molecular Mechanisms and Biological Functions of the Fas Pathway

Type Stratification, Signal Transduction, and Effector Networks of the Interferon (IFN) Pathway

How to Map the NF-κB Pathway and Choose Inhibitors: Bringing Inflammatory Transcriptional Output into a “Controllable Range” (Tables A–F)

Metabolic signaling pathway

Wnt/β-Catenin Signaling Pathway

Hedgehog Signaling

Alzheimer’s Disease Signaling