Tumor necrosis factor

Enhanceosome composition of human TNF.

Diagram of TNF exons and introns.

Tumor Necrosis Factor (TNF) is a cytokine involved in systemic inflammation and is part of the body's immune response. It is produced chiefly by activated macrophages, although it can be produced by other cell types such as lymphocytes, fibroblasts, and neurons. TNF is a member of a group of cytokines that stimulate the acute phase reaction.

Structure

Structure of a TNF monomer.

TNF is a trimeric protein, meaning it is composed of three identical subunits. Each subunit is a monomer that binds to the others to form the active cytokine. The TNF monomer is a compact, globular protein with a characteristic fold that is shared among members of the TNF superfamily.

Function

TNF plays a key role in regulating immune cells. It is able to induce fever, apoptosis (programmed cell death), cachexia (wasting syndrome), and inflammation. TNF is also involved in the regulation of cellular proliferation, differentiation, and death. It is a critical component of the inflammatory response and is involved in the pathogenesis of various diseases, including rheumatoid arthritis, inflammatory bowel disease, and psoriasis.

Receptors

TNF exerts its effects by binding to its receptors, TNFR1 and TNFR2.

TNFR1

TNFR1 cell signaling pathway.

TNFR1 is ubiquitously expressed and can be activated by both the membrane-bound and soluble forms of TNF. Upon activation, TNFR1 can initiate several signaling pathways, including the activation of NF-_B, which leads to the expression of genes involved in inflammation and survival.

TNFR2

TNFR2 cell signaling pathway.

TNFR2 is primarily expressed in immune cells and is activated mainly by the membrane-bound form of TNF. TNFR2 signaling is associated with the activation of anti-apoptotic pathways and the promotion of cell survival and proliferation.

Clinical Significance

Due to its role in inflammation and immune regulation, TNF is a target for therapeutic intervention in various inflammatory diseases. TNF inhibitors, such as infliximab, etanercept, and adalimumab, are used to treat conditions like rheumatoid arthritis, ankylosing spondylitis, and Crohn's disease. These inhibitors work by blocking the interaction of TNF with its receptors, thereby reducing inflammation and tissue damage.

Related Pages

• Cytokine
• Inflammation
• Rheumatoid arthritis
• Apoptosis

References

• Aggarwal, B. B., & Natarajan, K. (1996). Tumor necrosis factors: Developments during the last decade. European Cytokine Network, 7(2), 93-124.
• Balkwill, F. (2009). Tumour necrosis factor and cancer. Nature Reviews Cancer, 9(5), 361-371.