TNF Signaling Pathway: Receptor Layering Structure, Complex Conversion Mechanisms, and the Inflammation–Death Effector Network
TNF Signaling Pathway: Receptor Layering Structure, Complex Conversion Mechanisms, and the Inflammation–Death Effector Network
The TNF signaling pathway is one of the most central signaling networks in inflammatory responses, cell fate regulation, and tissue homeostasis maintenance. Its complexity is not reflected in the single fact that TNF can induce inflammation, but in that the same ligand stimulus can, under different receptor backgrounds, ubiquitination states, cellular metabolic conditions, and death checkpoint constraints, respectively lead to inflammatory amplification, survival maintenance, apoptosis, or necroptosis.
Keywords: TNF; TNFR1; TNFR2; RIPK1; NF-κB; MAPK; apoptosis; necroptosis; inflammatory signaling.
1 Basic framework of the TNF signaling pathway
1.1 Ligand and receptor system
(1) Forms of TNF
TNF usually refers to tumor necrosis factor alpha. Its initial form is a transmembrane protein, which can be released as soluble TNF after cleavage by metalloproteases. Both membrane TNF and soluble TNF have biological activity, but they are not completely identical in receptor affinity, local mode of action, and signaling strength. Membrane TNF is more likely to form efficient receptor clustering in cell-contact environments, whereas soluble TNF more often participates in systemic or local inflammatory expansion.
(2) Receptor classification
TNF mainly exerts its functions through two types of receptors, namely TNFR1 and TNFR2. TNFR1 is widely expressed in various immune cells and non-immune cells and is the core receptor mediating TNF-induced inflammatory and death signaling. TNFR2 expression is more restricted by cell type and is commonly found in regulatory T cells, endothelial cells, some myeloid cells, and certain activated lymphocytes. Its function is more inclined toward immune regulation, tissue repair, and signal amplification.
1.2 Core characteristics of the pathway
(1) Clear division of receptor function
TNFR1 contains a death domain and has the ability to connect inflammatory signaling with death signaling. TNFR2 does not contain a classical death domain and usually does not directly trigger apoptosis, but it can alter the inflammatory threshold and survival state of cells by recruiting molecules such as TRAF2.
(2) Highly branched signal output
After TNF stimulation, the cell is not directly determined to enter a death or survival state. Its early stage usually first forms a receptor-proximal signaling platform, and then diverges into different branches according to ubiquitination modification, kinase activity, transcriptional feedback, and the state of inhibitory molecules.
(3) The essence of the pathway lies in complex conversion
The most critical mechanism of the TNF signaling pathway does not lie in whether a single protein is upregulated, but in the dynamic conversion among Complex I, Complex II, and the necroptotic complex. In other words, the determining factor of the TNF signaling pathway lies in the state of the complex, rather than simply in whether the ligand is present.
2 TNFR1 receptor-proximal events
2.1 Assembly of Complex I
(1) Initial recruitment
After TNF binds TNFR1, the receptor cytoplasmic tail first recruits molecules such as TRADD, RIPK1, TRAF2, cIAP1, and cIAP2, forming a membrane-associated signaling platform, namely Complex I. This complex is not a death complex, but the starting node of TNF signal divergence.
(2) Scaffold function of RIPK1
In Complex I, RIPK1 initially mainly plays a scaffold role rather than a kinase role. It provides a platform for the subsequent recruitment of TAK1, the IKK complex, and linear ubiquitin chain-related molecules, and is the key center for establishing the inflammatory and survival branches.
2.2 Determining role of ubiquitination modification
(1) K63-linked ubiquitin chains
cIAP1 and cIAP2 can promote K63-linked ubiquitin chain modification of molecules such as RIPK1, thereby enhancing the stability of the signaling complex and providing binding sites for downstream kinase complexes.
(2) Linear ubiquitin chains
The LUBAC complex can further assemble linear ubiquitin chains at the receptor-proximal site. This process is particularly important for stable activation of the NF-κB pathway and is also an important protective link that prevents TNF signaling from prematurely shifting to the death branch.
(3) Mechanistic significance
Therefore, ubiquitination is not an accessory modification, but one of the most central direction-determining layers of the TNF signaling pathway. When ubiquitin chains are sufficiently established, cells are more likely to enter inflammatory and survival states; when ubiquitin chains are lost or unstable, the pathway is more likely to shift toward death programs.
3 TNFR1-mediated inflammatory and survival branches
3.1 Classical NF-κB branch
(1) Activation of the IKK complex
After Complex I is formed, TAK1 and the IKK complex are activated, promoting IκB degradation and thereby releasing NF-κB to enter the nucleus.
(2) Main transcriptional consequences
After NF-κB activation, it can induce the expression of various inflammatory- and survival-related genes, including TNF itself, IL-1, IL-6, chemokines, adhesion molecules, and multiple anti-apoptotic proteins.
(3) Functional positioning
This branch indicates that the initial dominant output after TNF stimulation is not death, but inflammatory amplification and cellular adaptation. Only when this protective layer cannot be established or is disrupted will the death program be released from inhibition.
3.2 MAPK branch
(1) Activation of JNK and p38
TNF can activate JNK and p38 through modules such as TAK1, thereby regulating stress responses, inflammatory gene expression, and post-transcriptional regulation.
(2) Participation of ERK
In some cell types, TNF can also affect the ERK branch and participate in proliferation, differentiation, and metabolic remodeling.
(3) Biological significance
The MAPK branch is not an accessory phenomenon of NF-κB, but an important component by which TNF shapes inflammatory magnitude, duration, and tissue-specific effects.
3.3 Establishment of the survival program
(1) Induction of anti-apoptotic factors
NF-κB can induce the expression of molecules such as c-FLIP, BCL2 family members, cIAP, and A20. These molecules together constitute the death buffering layer after TNF signaling.
(2) Checkpoint property
As long as this buffering layer remains intact, cells may not necessarily enter the death program even if continuously exposed to a TNF environment. Therefore, TNF-induced death is essentially a secondary result after checkpoint imbalance.
4 TNFR1-mediated apoptotic branch
4.1 Conditions for the formation of Complex II
(1) Destabilization of Complex I
When RIPK1 ubiquitination is insufficient, LUBAC function declines, TAK1 is inactivated, IKK is impaired, or the cell cannot establish a sufficient NF-κB protective layer, receptor-proximal signaling will shift from a membrane-associated state to a cytosolic death platform.
(2) Components of Complex II
At this time, RIPK1, FADD, and caspase-8 can form Complex II. This complex is the core platform of TNF-related apoptosis.
4.2 Caspase-8-dependent programmed apoptosis
(1) Initiation process
After caspase-8 is activated, it can cleave and activate caspase-3 and caspase-7, driving the cell into classical programmed apoptosis.
(2) Morphological features
Cells show nuclear condensation, DNA fragmentation, cytoplasmic condensation, and apoptotic body formation, while membrane integrity is relatively preserved in the early stage.
(3) Mitochondrial amplification layer
In some cell types, caspase-8 can also cleave BID to generate tBID. After the latter translocates to mitochondria, it can promote changes in mitochondrial outer membrane permeability, thereby enhancing the activation of caspase-9 and effector caspases. Therefore, BID is an important bridge linking extrinsic death receptor apoptosis and the mitochondrial amplification branch.
5 TNFR1-mediated necroptotic branch
5.1 Background for the initiation of necroptosis
(1) Inhibition of caspase-8
When caspase-8 activity is inhibited, absent, or its upstream regulation is abnormal, TNF signaling cannot smoothly complete the apoptotic program and may instead shift toward necroptosis.
(2) Release of RIPK1 kinase activity
Under this condition, RIPK1 changes from a scaffold protein into a kinase-driven factor and forms a necroptosis-related complex with RIPK3.
5.2 RIPK3-MLKL axis
(1) Activation of RIPK3
After RIPK1 binds RIPK3, it promotes RIPK3 phosphorylation, thereby initiating the core kinase program of necroptosis.
(2) Phosphorylation and oligomerization of MLKL
Activated RIPK3 can phosphorylate MLKL. MLKL then oligomerizes and translocates to the cell membrane, causing membrane rupture and leakage of intracellular contents.
(3) Pathological significance
Necroptosis is different from classical apoptosis in that it has obvious pro-inflammatory properties, and therefore has a stronger pathological amplification effect in chronic inflammation, ischemia-reperfusion injury, neuroinflammation, and the tumor necrotic microenvironment.
Table 1 Main output directions of TNFR1 signaling
Output direction | Key complex or molecule | Main biological result |
Inflammation/survival | Complex I, TAK1, IKK, NF-κB, MAPK | Inflammatory gene expression, survival support, stress adaptation |
Apoptosis | Complex II, FADD, caspase-8, BID, caspase-3 | Programmed apoptosis and mitochondrial amplification |
Necroptosis | RIPK1, RIPK3, MLKL | Membrane rupture, pro-inflammatory cell death |
6 Characteristics of the TNFR2 signaling pathway
6.1 Receptor properties
(1) Does not directly connect to the death domain
Because TNFR2 does not contain a classical death domain, it usually does not directly initiate the FADD-caspase-8 axis.
(2) Focuses more on TRAF2-dependent signaling
TNFR2 more often activates NF-κB and related survival signaling through molecules such as TRAF2 and cIAP, mainly affecting cell expansion, activation, and immune regulation.
6.2 Immunological significance of TNFR2
(1) Association with regulatory T cells
TNFR2 has relatively high functional weight in regulatory T cells and can affect their expansion, homeostasis maintenance, and suppressive activity.
(2) Tissue repair and vascular-related responses
In some tissues, TNFR2 is also related to endothelial homeostasis, repair responses, and local cell survival.
6.3 Relationship between TNFR1 and TNFR2
(1) Not a simple opposition
TNFR1 and TNFR2 are not in a simple binary relationship in which one is pro-inflammatory and the other is anti-inflammatory. The two together determine the overall effect of TNF across different time scales and different cell populations.
(2) Resource competition and threshold regulation
Recruitment of molecules such as TRAF2 and cIAP by TNFR2 may also indirectly alter the bias of TNFR1 toward death and inflammatory branches, so there is an obvious dynamic coupling relationship between the two receptor axes.
7 Key regulatory layers of the TNF pathway
7.1 Deubiquitination regulation
(1) CYLD
CYLD can remove ubiquitin chain modifications from molecules such as RIPK1, thereby weakening the stability of Complex I and increasing the tendency to initiate the death branch.
(2) A20
A20 has both deubiquitinating and ubiquitin-editing functions and is an important negative regulatory factor restricting excessive inflammatory and death outputs of TNF.
(3) OTULIN
OTULIN mainly regulates linear ubiquitin chain homeostasis and has an important impact on the integrity of LUBAC-related signaling.
7.2 Dual properties of RIPK1
(1) Scaffold function
In the inflammatory and survival branches, RIPK1 mainly exists as a scaffold molecule.
(2) Kinase function
Under death conditions, the kinase activity of RIPK1 becomes a key factor driving necroptosis and the formation of some death complexes.
(3) Methodological implication
Therefore, merely detecting RIPK1 protein expression is far from sufficient. More importantly, it is necessary to distinguish the complex state in which it resides and whether it has entered the kinase-driven mode.
8 Main biological functions of the TNF signaling pathway
8.1 Inflammatory amplification
(1) Cascade amplification of cytokines
TNF can upregulate the expression of multiple cytokines, chemokines, and adhesion molecules and is an important upstream factor for amplification of the inflammatory microenvironment.
(2) Endothelial activation
TNF can promote vascular endothelial cells to enter a pro-adhesive and pro-permeable state, creating conditions for inflammatory cell recruitment.
8.2 Cell fate regulation
(1) Survival maintenance
When the protective layer is intact, TNF can maintain cell survival, enhance stress adaptation, and remodel transcriptional programs.
(2) Death execution
When checkpoints are imbalanced, TNF can shift into apoptosis or necroptosis, so its essence is a cell fate divergence platform.
8.3 Tissue homeostasis and remodeling
(1) Acute response
In acute injury, TNF can promote the clearance of damaged cells and the initiation of tissue repair.
(2) Chronic injury
If TNF remains highly expressed, it may promote chronic inflammation, tissue destruction, fibrosis, and pathological remodeling.
9 TNF signaling pathway and disease
9.1 Autoimmune and chronic inflammatory diseases
(1) Rheumatoid arthritis
TNF is an important driving factor in synovial inflammation, cartilage destruction, and bone erosion.
(2) Inflammatory bowel disease
TNF participates in the maintenance of intestinal mucosal inflammation, epithelial barrier disruption, and imbalance of the local immune network.
(3) Psoriasis and spondyloarthropathy
TNF plays a key role in abnormal responses of skin keratinocytes, enthesis inflammation, and chronic tissue remodeling.
9.2 Infection-related diseases
(1) Role in host defense
TNF participates in macrophage activation, granuloma formation, and the organization of inflammation in the early stage of infection.
(2) Therapeutic risk implication
This is also an important mechanistic basis for the increased risk of infections such as tuberculosis during anti-TNF therapy.
9.3 Tumors and the tumor microenvironment
(1) Bidirectional properties
In some contexts, TNF can promote tumor cell death and immune clearance, whereas in other contexts it can maintain chronic inflammation, abnormal vasculature, and an immunosuppressive microenvironment.
(2) Context dependence
Therefore, TNF cannot be simply classified as either a tumor-promoting factor or a tumor-suppressive factor. Its true effect must be comprehensively analyzed in the context of a specific tissue and microenvironment.
10 Experimental research and result interpretation of the TNF signaling pathway
10.1 Common observation indicators
(1) Receptor-level indicators
The expression profiles of TNFR1 and TNFR2 are prerequisites for determining the basis of cellular response.
(2) Proximal complex-level indicators
TRADD, RIPK1, TRAF2, cIAP1/2, and their ubiquitination states are key readouts for determining the initial branch direction of the pathway.
(3) Inflammatory branch-level indicators
IκB degradation, p65 nuclear translocation, JNK and p38 activation, and inflammatory gene expression are the main indicators of the inflammation/survival branch.
(4) Death branch-level indicators
Caspase-8, BID, caspase-3, caspase-9, and RIPK3, MLKL, and their cleavage or phosphorylation states are the core indicators for interpretation of apoptosis and necroptosis.
10.2 Common experimental strategies
(1) TNF single-stimulation model
Suitable for observing the inflammation/survival main axis and early proximal events.
(2) TNF combined with CHX model
Can weaken the transcription-dependent protective layer and is more likely to reveal the apoptotic branch.
(3) TNF combined with caspase inhibitor model
Can promote pathway switching from apoptosis to necroptosis and is more conducive to observing the RIPK1-RIPK3-MLKL axis.
(4) Genetic intervention model
By knocking down or knocking out molecules such as RIPK1, caspase-8, BID, RIPK3, MLKL, and TRAF2, the relationships among different levels can be dissected.
10.3 Common interpretation biases
(1) Simply understanding TNF as a pro-inflammatory factor
The most central feature of TNF is not inflammation itself, but its ability to connect inflammation, survival, and death through complex conversion.
(2) Viewing death as an intrinsic output
In most cells, the initial dominant output after TNF stimulation is inflammation and establishment of the protective layer, rather than immediate entry into the death program.
(3) Ignoring receptor differences
If TNFR1 and TNFR2 are not distinguished, it is often difficult to accurately determine the source of signaling and the terminal effect in a specific experimental system.
Table 2 Key readouts for experimental analysis of the TNF signaling pathway
Observation level | Common indicators | Methodological significance |
Receptor level | TNFR1, TNFR2 | Determine the basis of response |
Proximal complex level | TRADD, RIPK1, TRAF2, cIAP1/2, ubiquitination state | Determine the branch starting point |
Inflammatory branch level | IκB, NF-κB, JNK, p38 | Determine inflammation and survival outputs |
Apoptotic branch level | FADD, caspase-8, BID, caspase-3, caspase-9 | Determine programmed apoptosis and mitochondrial amplification |
Necroptosis level | RIPK3, MLKL | Determine necroptotic output |
11 Product tables related to the TNF signaling pathway
11.1 Product table of ligands, receptors, and upstream regulatory layers of the TNF signaling pathway
Catalog No. | Name | Grade and Purity | Applicable research direction/use |
Anti-Mouse TNF alpha Antibody | ≥95% | Suitable for mouse TNFα neutralization and functional blocking experiments | |
TNF alpha Armenian Hamster mAb | Carrier Free,Azide Free,Validated,PBS Only,≥95%(SDS-PAGE),See COA | Suitable for TNFα detection and blocking studies | |
TNF alpha Mouse mAb | Animal Free,Carrier Free,ExactAb™,Azide Free,Validated,High Performance,PBS Only,≥95%(SDS-PAGE),1.0 mg/mL | Suitable for TNFα detection | |
TNF alpha Mouse mAb | Animal Free,Carrier Free,ExactAb™,Azide Free,Validated,High Performance,PBS Only,≥95%(SDS-PAGE),0.5 mg/mL | Suitable for TNFα detection | |
TNF alpha Mouse mAb | Animal Free,Carrier Free,ExactAb™,Azide Free,Validated,High Performance,PBS Only,≥95%(SDS-PAGE),1.0 mg/mL | Suitable for TNFα detection | |
TNF Receptor I/CD120a Armenian Hamster mAb | Carrier Free,ExactAb™,Low Endotoxin,Azide Free,Validated,PBS Only,≥95%(SDS-PAGE&HPLC),See COA | Suitable for TNFR1/CD120a detection and receptor-level analysis | |
TNF Receptor II/CD120b Armenian Hamster mAb | Carrier Free,ExactAb™,Low Endotoxin,Azide Free,Validated,PBS Only,≥95%(SDS-PAGE&HPLC),See COA | Suitable for TNFR2/CD120b detection and receptor-level analysis | |
TNF Receptor II/CD120b Rat mAb | Carrier Free, ExactAb™, Validated, See COA | Suitable for TNFR2/CD120b detection | |
TAPI-0 (TNF alpha processing inhibitor-0) | ≥95% | Suitable for inhibiting TNFα precursor processing and release and studying upstream regulation of TNF generation | |
Recombinant TNF Alpha Induced Protein 8 Antibody | KD Validation | Suitable for TNFAIP8 detection and analysis of the TNF-induced regulatory layer | |
Human TNF Alpha Induced Protein 8 Like 2 (TIPE2) ELISA Kit | BioReagent | Suitable for quantitative detection of the TNF-related negative regulatory molecule TIPE2 |
11.2 Product table of the apoptosis initiation and BID amplification layer of the TNF signaling pathway
Catalog No. | Name | Grade and Purity | Applicable research direction/use |
BID Human Pre-designed siRNA Set A |
| Suitable for BID gene silencing and validation of mitochondrial amplification in TNF-induced apoptosis | |
BID Mouse mAb | Animal Free,Carrier Free,ExactAb™,Azide Free,Validated,High Performance,PBS Only,≥95%(SDS-PAGE),1.0 mg/mL | Suitable for total BID protein detection | |
BID Mouse mAb | Carrier Free,ExactAb™,Azide Free,Validated,High Performance,PBS Only,≥95%(SDS-PAGE),1.0 mg/mL | Suitable for total BID protein detection | |
BID Mouse mAb | KD Validation | Suitable for BID expression validation | |
BID Mouse mAb | KD Validation | Suitable for BID expression validation | |
Recombinant BID Antibody | Animal Free,Carrier Free,Recombinant,ExactAb™,Azide Free,Validated,High Performance,PBS Only,≥95%(SDS-PAGE),1.0 mg/mL | Suitable for BID detection | |
Recombinant Bid Antibody | Recombinant, ExactAb™, Validated, See COA | Suitable for BID detection | |
pLenti-BID-sgRNA |
| Suitable for BID knockout validation and protein detection controls | |
pLenti-BID-sgRNA |
| Suitable for BID knockout validation and RNA detection controls | |
Bid BH3 (80-99) |
| Suitable for functional study of the BID BH3 domain | |
Bid BH3 (80-99), FAM labeled |
| Suitable for BID BH3 binding and fluorescence analysis | |
Bid BH3 peptide |
| Suitable for functional study of the BID mitochondrial amplification layer | |
r8 Bid BH3 |
| Suitable for intracellular delivery-type functional study of BID BH3 | |
tBID | ≥98% | Suitable for study of truncated BID-related apoptotic amplification | |
tBID | 10mM in DMSO | Suitable for functional validation of tBID in cell experiments | |
Recombinant Human BID Protein | ActiBioPure™, Bioactive, Carrier Free, ≥95%(SDS-PAGE) | Suitable for in vitro functional study of BID | |
Recombinant Mouse BID Protein | Carrier Free,≥95%(SDS-PAGE),expressed in E. coli; See COA | Suitable for functional study of mouse BID | |
Recombinant Mouse Bid Protein | ≥90%(SDS-PAGE) | Suitable for functional study of mouse BID | |
Human BH3 Interacting Domain Death Agonist (Bid) ELISA Kit | BioReagent | Suitable for quantitative detection of human BID | |
Mouse BH3 Interacting Domain Death Agonist (Bid) ELISA Kit | BioReagent | Suitable for quantitative detection of mouse BID |
11.3 Product table of the caspase initiation and execution layer of the TNF signaling pathway
Catalog No. | Name | Grade and Purity | Applicable research direction/use |
Caspase 8 Mouse mAb | KD Validation | Suitable for total Caspase-8 protein detection | |
Cleaved Caspase 8 Antibody | KD Validation | Suitable for detection of cleaved Caspase-8 and is an important readout of TNF extrinsic apoptosis initiation | |
Recombinant Caspase 8 Antibody | KD Validation | Suitable for Caspase-8 detection | |
Recombinant Caspase 8 Antibody | KD Validation | Suitable for Caspase-8 detection | |
Recombinant Caspase-8 Antibody | Recombinant, ExactAb™, Validated, Lot by Lot | Suitable for Caspase-8 detection | |
Recombinant Human Caspase-8 Protein | Carrier Free,His Tag,≥90%(SDS-PAGE) | Suitable for enzymatic and mechanistic study of Caspase-8 | |
Caspase 8 Activity Assay Kit | BioReagent | Suitable for detection of Caspase-8 activation | |
Caspase 8 Activity Assay Kit | BioReagent,Suitable for Analysis, Colorimetry | Suitable for colorimetric detection of Caspase-8 activity | |
Caspase-8 inhibitor II | ≥98% | Suitable for validating the dependence of TNF-induced apoptosis on Caspase-8 | |
Caspase 3 Mouse mAb | Carrier Free,ExactAb™,Azide Free,Validated,High Performance,PBS Only,≥95%(SDS-PAGE),1.0 mg/mL | Suitable for total Caspase-3 protein detection | |
Caspase 3 Mouse mAb | Carrier Free,ExactAb™,Azide Free,Validated,High Performance,PBS Only,≥95%(SDS-PAGE),1.0 mg/mL | Suitable for total Caspase-3 protein detection | |
Pro caspase 3 Antibody | KD Validation | Suitable for precursor Caspase-3 detection | |
Recombinant Caspase 3 Antibody | KD Validation | Suitable for Caspase-3 detection | |
Recombinant Caspase 3 Antibody | KD Validation | Suitable for Caspase-3 detection | |
Recombinant Caspase3 Antibody | ExactAb™, Validated, Recombinant, 0.9mg/mL | Suitable for Caspase-3 detection | |
Recombinant active + pro caspase 3 Antibody | KD Validation | Suitable for combined detection of active and precursor Caspase-3 | |
Caspase 3 Activity Assay Kit | BioReagent | Suitable for detection of executioner apoptosis | |
Caspase 3 Activity Assay Kit | BioReagent,Suitable for Analysis, Colorimetry | Suitable for colorimetric detection of Caspase-3 activity | |
Caspase 3/7 Activity Assay Kit | BioReagent | Suitable for detection of terminal activation of executioner apoptosis | |
Caspase-3/7 Inhibitor | ≥97% | Suitable for validating the dependence of TNF-induced cell death on executioner caspases | |
Caspase-3-IN-1 | Moligand™, 10 mM in DMSO | Suitable for Caspase-3 inhibition studies | |
Caspase-9 Mouse mAb | ExactAb™, Validated, 2.05 mg/mL | Suitable for Caspase-9 detection | |
Caspase-9 Mouse mAb | Carrier Free,ExactAb™,Azide Free,Validated,High Performance,PBS Only,≥95%(SDS-PAGE),1.0 mg/mL | Suitable for Caspase-9 detection | |
Recombinant Caspase 9 Antibody | KD Validation | Suitable for Caspase-9 detection | |
Recombinant Caspase-9 Antibody | Recombinant, ExactAb™, Validated, See COA | Suitable for Caspase-9 detection | |
Recombinant cleaved Caspase-9 Antibody | KD Validation | Suitable for detection of cleaved Caspase-9, reflecting activation of the mitochondrial amplification branch | |
Caspase-9 substrate (chromogenic) | ≥98% | Suitable for Caspase-9 activity analysis | |
Caspase 9 Activity Assay Kit | BioReagent,Suitable for Analysis, Colorimetry | Suitable for colorimetric detection of Caspase-9 activity | |
Caspase-9 Inhibitor III | ≥95% | Suitable for validating the dependence of the TNF-BID axis on the mitochondrial amplification branch | |
Z-VAD(OH)-FMK (Caspase Inhibitor VI) | 10mM in DMSO | Suitable for pan-caspase blockade and commonly used in studies of conversion between the TNF death branch and necroptosis | |
Z-VAD(OH)-FMK (Caspase Inhibitor VI) | ≥97% | Suitable for pan-caspase blockade studies |
11.4 Product table of apoptosis functional detection in the TNF signaling pathway
Catalog No. | Name | Grade and Purity | Applicable research direction/use |
aladdin™ 488 caspase-3 live cell assay kit |
| Suitable for dynamic detection of Caspase-3 in live cells | |
Live Cell Caspase-3/7 Activity and Annexin V Dual Apoptosis Detection Kit (LumiDye™ 488 Caspase-3/7, LumiDye™ 594-Annexin V, Hoechst 33342) | BioReagent,Biological Stain, for fluorescence analysis, for microscopy, sterile | Suitable for real-time detection of TNF-induced apoptosis | |
Live Cell Caspase-3/7 Activity and Annexin V Dual Apoptosis Detection Kit (LumiDye™ 488 Caspase-3/7, LumiDye™ 647-Annexin V, EthD Gold) | BioReagent,Biological Stain, for fluorescence analysis, for microscopy, sterile | Suitable for dual-parameter detection of apoptosis | |
Live Cell Caspase-3/7 Activity and Annexin V Dual Apoptosis Detection Kit (LumiDye™ 488 Caspase-3/7, LumiDye™ 647-Annexin V, EthD Gold, Hoechst 33342) | BioReagent,Biological Stain, for fluorescence analysis, for microscopy, sterile | Suitable for combined analysis of apoptosis and membrane integrity | |
Live Cell Caspase-3/7 Activity and Annexin V Dual Apoptosis Detection Kit (LumiDye™ 488 Caspase-3/7, LumiDye™ 647-Annexin V, Hoechst 33342) | BioReagent,Biological Stain, for fluorescence analysis, for microscopy, sterile | Suitable for real-time apoptosis detection | |
Human Caspase 3 (CASP3) ELISA Kit | BioReagent | Suitable for quantitative detection of human Caspase-3 | |
Human Caspase 7 (CASP7) ELISA Kit | BioReagent | Suitable for quantitative detection of human executioner caspases | |
Human Caspase 8 (CASP8) ELISA Kit | BioReagent | Suitable for quantitative detection of human Caspase-8 | |
Human Caspase 9 (CASP9) ELISA Kit | BioReagent | Suitable for quantitative detection of human Caspase-9 | |
Rat Caspase 3 (CASP3) ELISA Kit | BioReagent | Suitable for quantitative detection of rat Caspase-3 | |
Rat Caspase 7 (CASP7) ELISA Kit | BioReagent | Suitable for quantitative detection of rat Caspase-7 | |
Rat Caspase 8 (CASP8) ELISA Kit | BioReagent | Suitable for quantitative detection of rat Caspase-8 | |
Rat Caspase 9 (CASP9) ELISA Kit | BioReagent | Suitable for quantitative detection of rat Caspase-9 | |
Mouse Caspase 3 (CASP3) ELISA Kit | BioReagent | Suitable for quantitative detection of mouse Caspase-3 | |
Mouse Caspase 7 (CASP7) ELISA Kit | BioReagent | Suitable for quantitative detection of mouse Caspase-7 | |
Mouse Caspase 8 (CASP8) ELISA Kit | BioReagent | Suitable for quantitative detection of mouse Caspase-8 | |
Mouse Caspase 9 (CASP9) ELISA Kit | BioReagent | Suitable for quantitative detection of mouse Caspase-9 |
The core of the TNF signaling pathway is not a single inflammatory output, but a dynamic signaling network jointly shaped by receptor layering, complex conversion, and death checkpoints. Its most essential feature is that the same TNF stimulus can, under different conditions, lead to inflammatory maintenance, cell survival, apoptosis, or necroptosis.
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