IL1A - Interleukin-1 alpha | Elisa - Clia - Antibody - Protein

Background

Interleukin-1 alpha (IL-1α) is a pro-inflammatory cytokine belonging to the interleukin-1 (IL-1) family. It plays a crucial role in the regulation of immune responses, inflammation, and hematopoiesis. IL-1α is produced primarily by activated macrophages, but it can also be expressed by a variety of cell types including epithelial cells, endothelial cells, and fibroblasts. Unlike many other cytokines, IL-1α is unique in that it is active in both its membrane-bound precursor form and its cleaved secreted form. This dual functionality allows IL-1α to act locally at the site of synthesis as well as systemically.

Protein Structure

IL-1α is synthesized as a 31 kDa precursor protein consisting of:

• N-terminal pro-domain: This region remains attached in the membrane-bound form, contributing to local inflammatory signaling.
• C-terminal domain: The C-terminal 17 kDa mature form is generated after cleavage by calpain and other proteases, which can be secreted and exert systemic effects.

The mature IL-1α binds to the IL-1 receptor type 1 (IL-1R1), initiating a signaling cascade that results in the activation of nuclear factor kappa B (NF-κB) and mitogen-activated protein kinases (MAPKs).

Classification and Subtypes

IL-1α is a part of the broader IL-1 family, which includes several related cytokines such as IL-1β, IL-18, IL-33, and IL-36. IL-1α and IL-1β share similar functions and can bind to the same receptors, but they differ in their regulation and cellular sources.

Function and Biological Significance

IL-1α plays multiple roles in the immune system:

• Inflammatory Response: IL-1α is a key mediator of the inflammatory response, inducing the production of other cytokines, chemokines, and adhesion molecules that facilitate leukocyte recruitment to sites of infection or injury.
• Fever Induction: It acts on the hypothalamus to induce fever, an important component of the acute phase response to infection.
• Cellular Proliferation and Differentiation: IL-1α influences the proliferation and differentiation of various cell types, including T cells and hematopoietic progenitor cells.
• Tissue Homeostasis and Repair: It is involved in tissue repair processes and maintaining homeostasis, particularly in epithelial tissues.

Clinical Issues

Dysregulation of IL-1α is associated with a variety of pathological conditions:

• Chronic Inflammatory Diseases: Elevated levels of IL-1α are implicated in chronic inflammatory diseases such as rheumatoid arthritis, inflammatory bowel disease (IBD), and psoriasis.
• Cancer: IL-1α can contribute to tumor progression by promoting a pro-inflammatory tumor microenvironment, enhancing angiogenesis, and facilitating tumor cell invasion and metastasis.
• Infection: While IL-1α is crucial for host defense, excessive or prolonged production can lead to detrimental effects during severe infections or sepsis.

Summary

Interleukin-1 alpha (IL-1α) is a critical cytokine involved in the regulation of inflammatory and immune responses. It functions both as a membrane-bound precursor and as a cleaved secreted protein, allowing it to act locally and systemically. IL-1α plays vital roles in mediating inflammation, inducing fever, and promoting cellular proliferation and differentiation. Dysregulation of IL-1α is linked to various chronic inflammatory diseases, cancer, and infection-related complications. Understanding the mechanisms of IL-1α signaling and its role in disease can provide insights into potential therapeutic targets for treating inflammatory conditions and related disorders.