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IL-33 (Interleukin 33)

Interleukin 33 (IL-33) is a  that in humans is encoded by the IL33 gene.

Interleukin 33 is a member of the IL-1 family that potently drives production  of T helper (Th2)-cytokines.

IL33 is a ligand for the IL-1 family  receptor that is highly expressed on TH2 cells, mast cells, and group 2 innate lymphocytes.

IL-33 is expressed by a wide variety of cell types, including fibroblasts, mast cells dendritic cells, macrophages, endothelial cells, epithelial cells and osteoblasts.

IL-33 is a member of the IL-1 superfamily of cytokines,.

IL-33 induces helper T cells. Mast cells, eosinophils, and basophils to produce type 2 cytokines. 

IL-33 acts intracellularly as a nuclear factor and extracellularly as a cytokine.

Cytokine role

As a cytokine, IL-33 interacts with the receptors IL-Ra and IL-1 Receptor Accessory Protein (), activating intracellular molecules in the  and signaling pathways that drive production of type 2.

IL-33 is a dual function cytokine. 

IL-33 has been associated with several disease states: asthma, allergy, endometriosis, and hay fever. 

It is involved in allergic and parasite-induced inflammatory responses.

Besides its chromatin-associated function, it is constitutively expressed in healthy endothelial cells, because it acts as DAMPs (damage associated molecular proteins) after its release to extracellular space of cells in the context of immunologic not-silent cell death (necrosis or pyroptosis), and drives cytokine production in natural helper cells, nuocytes, Th2 lymphocytes, mast cells, basophils, eosinophils, invariant natural killer and natural killer T cells. 

It acts as a cytokine and signals inflammation in the body by acting upon macrophages, neutrophils, B cells, Th2 cells, eosinophils, basophils and mast cells. 

This protein is also thought to cause the itching that is associated with dermatitis, as it is located in keratinocytes and can communicate to nearby neurons initiating itching.

Elevated levels of IL-33 are associated with asthma, some cases of nonsmall cell lung carcinomas. 

Blocking of IL-33 reduced the growth of human nonsmall cell lung carcinomas. 

Normally, IL-33 is present in healthy intestinal tissue, but during inflammatory conditions its expression is increased. 

However, IL-33 has also a protective role under inflammatory conditions and is involved in wound healing.

In brain, IL-33 is expressed in oligodendrocytes and astrocytes and is implicated in the pathophysiology of intracerebral hemorrhage.

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