Interleukin 1 alpha

Interleukin 1 alpha (IL-1α) is a cytokine of the interleukin 1 family that plays a crucial role in the regulation of immune and inflammatory responses to infections or sterile insults. It is encoded by the IL1A gene in humans.

Structure

IL-1α is a member of the interleukin 1 family, which includes several other cytokines such as interleukin 1 beta (IL-1β) and interleukin 18 (IL-18). The IL-1α protein is initially synthesized as a 31 kDa precursor, which is then cleaved to produce a 17 kDa mature form. The precursor form of IL-1α is biologically active and can function as a pro-inflammatory cytokine.

Function

IL-1α is primarily produced by activated macrophages, but it can also be produced by other cell types such as keratinocytes, endothelial cells, and epithelial cells. It acts as a key mediator in the inflammatory response by inducing the expression of adhesion molecules, chemokines, and other pro-inflammatory cytokines.

Role in Inflammation

IL-1α binds to the interleukin 1 receptor, type I (IL-1RI), which is expressed on a variety of cell types. This binding triggers a signaling cascade that leads to the activation of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and mitogen-activated protein kinases (MAPKs), resulting in the transcription of genes involved in inflammation.

Role in Disease

IL-1α has been implicated in a variety of diseases, including autoimmune disorders, infectious diseases, and cancer. Elevated levels of IL-1α are associated with conditions such as rheumatoid arthritis, inflammatory bowel disease, and psoriasis.

Regulation

The activity of IL-1α is tightly regulated at multiple levels, including gene expression, precursor processing, and receptor antagonism. The interleukin 1 receptor antagonist (IL-1Ra) competes with IL-1α for binding to IL-1RI, thereby inhibiting its activity.

Clinical Significance

Due to its role in inflammation, IL-1α is a target for therapeutic intervention in inflammatory diseases. Anakinra, a recombinant form of IL-1Ra, is used to treat conditions such as rheumatoid arthritis by blocking the effects of IL-1α and IL-1β.

Research Directions

Ongoing research is focused on understanding the precise mechanisms by which IL-1α contributes to disease pathogenesis and exploring novel therapeutic strategies to modulate its activity. This includes the development of specific inhibitors and monoclonal antibodies targeting IL-1α.

See Also

• Interleukin 1 beta
• Cytokine
• Inflammation
• Autoimmune disease

External Links

• [UniProt entry for IL1A](https://www.uniprot.org/uniprot/P01583)
• [GeneCards entry for IL1A](https://www.genecards.org/cgi-bin/carddisp.pl?gene=IL1A)