TNF Gene

TNF gene (TNF stands for Tumor Necrosis Factor) is a protein-coding gene located on chromosome 6p21.33. The TNF gene encodes the multifunctional proinflammatory cytokine TNF-alpha, which belongs to the tumor necrosis factor (TNF) superfamily. This cytokine is secreted mainly by macrophages. TNF-alpha binds to its receptors TNFRSF1A (TNFR1) and TNFRSF1B (TNFBR), leading to their trimerization and activation. TNF-alpha is involved in the regulation of a wide range of biological processes, including cell proliferation, differentiation, apoptosis, lipid metabolism, and coagulation.

TNF-alpha is a potent pyrogen that causes fever by direct action or by stimulating interleukin-1 secretion and is involved in triggering cachexia. Under certain conditions, it can stimulate cell proliferation and induce cell differentiation. Impairs regulatory T cell (Treg) function in individuals with rheumatoid arthritis by dephosphorylating FOXP3. Increases the expression of protein phosphatase 1 (PP1), which dephosphorylates FOXP3, thereby inactivating FOXP3 and impairing Treg cell function. TNF-alpha induces insulin resistance in adipocytes by inhibiting insulin-induced IRS1 tyrosine phosphorylation and insulin-induced glucose uptake. The cytokine induces GKAP42 protein degradation in adipocytes, which is partly responsible for TNF-induced insulin resistance. It also plays a role in angiogenesis by inducing VEGF production synergistically with interleukin-1B and interleukin-6.

TNF-alpha is associated with a variety of diseases, including autoimmune diseases, insulin resistance, psoriasis, rheumatoid arthritis, ankylosing spondylitis, tuberculosis, autosomal dominant polycystic kidney disease and various types of tumors.

Mutations in this gene influence susceptibility to cerebral malaria, septic shock, Alzheimer's disease and rheumatic diseases (see also psoriatic arthritis).

1. Kusuhara K et al (2004) Tumor necrosis factor receptor-associated periodic syndrome with a novel mutation in the TNFRSF1Agene in a Japanese family. Eur J Pediatr 163: 30-32
2. Takada K et al (2003) Favorable preliminary experience with etanercept in two patients with the hyperimmunoglobulinemia D and periodic fever syndrome. Arthritis Rheum 48: 2645-2651
3. Toro JR (2000) Tumor necrosis factor receptor-associated periodic syndrome. Arch Dermatol 136: 1487-1494
4. Williamson LM, Hull D, Mehta R, Reeves WG, Robinson BHB, Toghill PJ (1982) Familial hibernian fever. Quart J Med 51: 469-480