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IL-1 Family & Receptor

IL-1 Family & Receptor

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    IL-1 Family & Receptor Background

    The Interleukin-1 superfamily & Interleukin-1 receptor family plays critical roles in initiating and promoting the host response to injury or infection, including fever, sleep, acute phase protein synthesis, chemokine production, adhesion molecule up-regulation and production and release of matrix metalloproteinases and growth factors. The original members of the Interleukin-1 superfamily are IL-1α, IL-1β, and the IL-1 receptor antagonist (IL-1RA).

    Interleukin-1 activity resides in IL-1α and IL-1β, which act by binding to a common receptor composed of a ligand binding chain, the type I IL-1 receptor, and a required signaling component, the IL-1 receptor accessory protein (AcP). The IL-1 receptor antagonist (IL-1RA) was described the third member of the family, which also binds to the type I IL-1 receptor but fails to bring about the subsequent interaction with AcP. IL-1RA competes for receptor binding with IL-1α and IL-1β, blocking their role in immune activation. Additional regulation is provided by the IL-1 receptor, which binds and sequesters the agonist IL-1s (especially IL-1β) without inducing any signaling response of its own.

    Six additional members of this family have since been described: IL-1F5, IL-1F6, IL-1F7, IL-1F8, IL-1F9, IL-1F10, with structural homology to IL-1α, IL-1β or IL-1RA. Another molecule described as a member of Interleukin-1 superfamily is IL-18. Recently, a further putative member of the Interleukin-1 superfamily has been described that is called IL-33.

    IL-1α and IL-1β are produced as precursor peptides. Mature IL-1β is released from Pro-IL-1β following cleavage by caspase-1 protein or the interleukin-1 converting enzyme (ICE). The three-dimensional structure of the mature forms of each member of the human Interleukin-1 superfamily is composed of 12-14 β-strands producing a barrel-shaped protein.

    The IL-1R/TLR Family encompasses the Ig domain family (IL-1 receptors, IL-18 receptors, and IL-1R-like receptors), the Toll-like receptors (TLR) and similar receptors, and a series of TIR domain-containing intracellular adapter molecules. These related receptors all have sequence similarity in their intracellular regions, which has thus been termed the Toll-IL-1 receptor (TIR) domain.

    IL-1 Family & Receptor References

    1. Boraschi D, et al. (2006) The interleukin-1 receptor family. Vitam Horm. 74:229-54.
    2. Ischenko AM, et al. (2007) IL-1 receptor antagonist as an aerosol in inflammation. J Aerosol Med. 20(4):445-59.
    3. Guo L, et al. (2009) IL-1 family members and STAT activators induce cytokine production by Th2, Th17, and Th1 cells. Proc Natl Acad Sci U S A. 106(32):13463-8.
    4. Bujak M, et al. (2009) The role of IL-1 in the pathogenesis of heart disease. Arch Immunol Ther Exp (Warsz). 57(3):165-76.