IL33 - Interleukin 33| Elisa - Clia - Antibody - Protein

Background

Interleukin 33 (IL-33) is a member of the IL-1 cytokine family and functions as an alarmin, which means it is released upon cellular damage to alert the immune system to tissue injury or infection. IL-33 is primarily expressed in the nuclei of various structural cells, including endothelial cells, epithelial cells, fibroblasts, and some immune cells. Unlike other cytokines, IL-33 is pre-formed and stored in the nucleus, where it binds to chromatin. Upon cellular damage or necrosis, IL-33 is rapidly released into the extracellular space, where it can exert its pro-inflammatory effects. It binds to the ST2 receptor (a member of the IL-1 receptor family), triggering a signaling cascade that involves MyD88, IRAKs, and TRAF6, leading to the activation of NF-κB and MAPKs pathways. This ultimately results in the production of various pro-inflammatory cytokines and chemokines.

Protein Structure

IL-33 is synthesized as a 30 kDa precursor protein, consisting of:

• N-terminal domain: This domain is responsible for the nuclear localization and chromatin binding of IL-33.
• C-terminal domain: The C-terminal domain of IL-33 contains the cytokine activity and is released extracellularly upon cleavage by caspases or other proteases.

The full-length precursor form can act intracellularly in the nucleus, while the cleaved form acts extracellularly by binding to the ST2 receptor.

Classification and Subtypes

IL-33 belongs to the IL-1 cytokine family, which also includes IL-1α, IL-1β, IL-18, and IL-36. The ST2 receptor exists in two forms: a membrane-bound form (ST2L) which mediates signaling, and a soluble form (sST2) which acts as a decoy receptor, modulating the availability and activity of IL-33.

Function and Biological Significance

IL-33 plays several key roles in the immune system:

• Mediator of Inflammation: IL-33 promotes the production of pro-inflammatory cytokines and chemokines, enhancing the recruitment and activation of various immune cells, including Th2 cells, mast cells, eosinophils, and basophils.
• Th2 Response: IL-33 is a potent inducer of Th2 immune responses, contributing to allergic inflammation and defense against parasitic infections.
• Tissue Homeostasis and Repair: IL-33 contributes to tissue repair processes by promoting the activation and recruitment of immune cells to damaged tissues.
• Regulation of Immune Responses: IL-33 can act both as a pro-inflammatory cytokine and as an immune regulatory molecule, depending on the context of its release and the receptors involved.

Clinical Issues

Dysregulation of IL-33 is implicated in various pathological conditions:

• Allergic Diseases: Elevated levels of IL-33 are associated with allergic diseases such as asthma, atopic dermatitis, and allergic rhinitis.
• Autoimmune Diseases: IL-33 has been implicated in the pathogenesis of autoimmune diseases such as rheumatoid arthritis, systemic lupus erythematosus, and inflammatory bowel disease.
• Cardiovascular Diseases: IL-33 and its receptor ST2 are involved in cardiovascular diseases, including myocardial infarction and heart failure, where they play roles in cardiac remodeling and inflammation.
• Infectious Diseases: IL-33 is involved in the immune response to various infections, enhancing the production of cytokines that help in the clearance of pathogens.

Summary

Interleukin 33 (IL-33) is a multifunctional cytokine belonging to the IL-1 family, playing critical roles in immune and inflammatory responses. It functions as an alarmin, alerting the immune system to tissue damage and promoting inflammation. IL-33 binds to the ST2 receptor, activating signaling pathways that result in the production of pro-inflammatory mediators. Dysregulation of IL-33 is linked to a variety of diseases, including allergic, autoimmune, cardiovascular, and infectious diseases. Understanding the mechanisms and roles of IL-33 in health and disease provides valuable insights into potential therapeutic targets for treating related conditions.