Human TNF-α
Tumor necrosis factor alpha (TNF-α) is a pro-inflammatory cytokine central to immune responses and a major therapeutic target for autoimmune diseases.
Human TNF-α
Function
Tumor necrosis factor alpha (TNF-α) is a pro-inflammatory cytokine that plays a central role in systemic inflammation and is a key mediator of the acute phase response. Originally identified for its ability to induce tumor necrosis, TNF-α is now recognized as a pleiotropic cytokine with diverse functions in immunity, inflammation, apoptosis, and cellular proliferation. It is primarily produced by activated macrophages, though many other cell types can produce TNF-α under inflammatory conditions.Biological Functions
Inflammatory Responses
- Acute Inflammation: Initiates and amplifies inflammatory cascades
- Endothelial Activation: Promotes expression of adhesion molecules and chemokines
- Leukocyte Recruitment: Attracts neutrophils, monocytes, and lymphocytes to sites of inflammation
- Fever Induction: Acts as an endogenous pyrogen
Immune System Modulation
- Macrophage Activation: Enhances antimicrobial and tumoricidal activities
- T Cell Activation: Provides costimulatory signals for T cell proliferation
- B Cell Function: Modulates antibody production and class switching
- NK Cell Activity: Enhances natural killer cell cytotoxicity
Pathological Roles
- Autoimmune Diseases: Excessive TNF-α drives pathology in rheumatoid arthritis, Crohn’s disease, psoriasis
- Sepsis: Contributes to septic shock and multiple organ failure
- Cancer: Dual role as both tumor promoter and suppressor
- Neuroinflammation: Involved in neurodegenerative diseases
Target Details
Protein Information
Protein Information
Organism: Homo sapiens (Human)
Gene Name: TNF
Alternative Names: Tumor necrosis factor, cachectin, TNF-alpha
Protein Family: TNF superfamily
Database References
Database References
UniProt ID: P01375
Gene ID: 7124
NCBI Reference: P01375-1
Protein Region: Val 77 - Leu 233 (mature protein)
Structural Information
Structural Information
Molecular Weight: ~17 kDa (monomer), ~51 kDa (trimer)
Structure: Beta-sandwich fold, forms stable homotrimers
Key Features: TNF homology domain, receptor binding sites
Active Form: Homotrimer (most biologically active form)
Receptors and Signaling
Receptors and Signaling
Primary Receptors: TNFR1 (p55, CD120a) and TNFR2 (p75, CD120b)
Signaling Pathways: NF-κB, MAPK, death receptor pathways
Cellular Effects: Inflammation, apoptosis, survival, proliferation
Regulation: Soluble receptors, binding proteins, protease cleavage
Therapeutic Relevance
Anti-TNF Therapies
TNF-α is one of the most successful therapeutic targets in modern medicine:- Monoclonal Antibodies: Infliximab, adalimumab, golimumab, certolizumab pegol
- Soluble Receptors: Etanercept (TNFR2-Fc fusion protein)
- Clinical Applications: Rheumatoid arthritis, ankylosing spondylitis, psoriasis, Crohn’s disease, ulcerative colitis
- Market Impact: Multi-billion dollar market for TNF inhibitors
Research Applications
Drug Development
- Inhibitor Screening: Identifying new TNF-α antagonists
- Biosimilar Development: Developing generic versions of anti-TNF biologics
- Next-Generation Therapeutics: Improved selectivity and reduced side effects
- Combination Therapies: TNF blockade with other immunomodulatory agents
Biomarker Studies
- Disease Activity: TNF-α levels correlate with disease severity in many conditions
- Treatment Monitoring: Tracking therapeutic response to anti-TNF therapy
- Drug Levels: Measuring therapeutic antibody concentrations
- Immunogenicity: Detecting anti-drug antibodies
Basic Research
- Inflammatory Mechanisms: Understanding TNF-α signaling pathways
- Disease Models: Studying TNF-α in animal models of human disease
- Cellular Biology: TNF-α effects on different cell types
- Immune Regulation: Role in adaptive and innate immunity
Clinical Applications
Established Indications
- Rheumatoid Arthritis: First and most successful application
- Inflammatory Bowel Disease: Crohn’s disease and ulcerative colitis
- Psoriasis: Both skin and joint manifestations
- Ankylosing Spondylitis: Spinal inflammation and stiffness
Emerging Applications
- Uveitis: Inflammatory eye disease
- Hidradenitis Suppurativa: Chronic skin condition
- Behçet’s Disease: Multi-system inflammatory disorder
- COVID-19: Potential role in cytokine storm management
Safety Considerations
- Infection Risk: Increased susceptibility to bacterial and viral infections
- Malignancy: Potential increased cancer risk with long-term use
- Autoimmunity: Paradoxical development of autoimmune conditions
- Cardiovascular: Effects on heart failure and cardiovascular risk
TNF-α plays crucial roles in host defense against infections. Anti-TNF therapies can significantly increase infection risk, particularly for tuberculosis and other opportunistic infections. Careful patient screening and monitoring are essential.
TNF-α is available in our target library as both the full-length trimer (most biologically relevant) and as monomeric forms for specialized applications. The trimeric form is recommended for most binding studies as it represents the physiologically active state.