Open AccessNUCLEAR FUNCTION AND RELEASE OF IL-33
Author(s) -
Mousa Komai Koma
Publication year - 2014
Publication title -
the professional medical journal/the professional medical journal
Language(s) - English
Resource type - Journals
eISSN - 2071-7733
pISSN - 1024-8919
DOI - 10.29309/tpmj/2014.21.03.2135
Subject(s) - interleukin 33 , autocrine signalling , microbiology and biotechnology , cytokine , paracrine signalling , secretion , receptor , immunology , biology , interleukin , medicine , endocrinology , biochemistry
Interleukin-33 (IL-33) is the most attractive novel cytokine identified as an IL-1family member. IL-33 was first named NF-HEV (nuclear factor from high endothelial venules), as itwas known to interact with nuclear chromatin although its exact intracellular functions are still tobe clarified. IL-33 is now recognized as the specific ligand for the orphan IL-1 receptor familymember ST2 and to be involved in polarization of T cells towards T helper 2-cell phenotype and inactivation of mast cells, basophils, eosinophils and natural killer cells. It is essential for IL-33 to beextracellularly released in order to bind to the ST2 receptor and consequently play a crucial role ininflammatory, infectious and autoimmune diseases. However, like the IL-1 family members, IL-1beta and IL-18, IL-33 mRNA is translated without a signal sequence for secretion. Additionally, IL-33 cannot be released by the processing and secretion mechanism shared by IL-1beta and IL-18as IL-33 is not a substrate of caspase-1 and does not require proteolysis for activation. In contrast,IL-33 can be inactivated by apoptotic caspases. Accordingly, IL-33 is proposed to be released asan alarmin from necrotic cells but deleted during apoptosis. Besides the known autocrine,paracrine mechanisms of cellular interaction with cytokines, release by necrotic cells is anotherpathway for a cytokine to display its function, which we suggest might be called 'necrocrine'.