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Direct Induction of Arginase I and Cytokines by IL‐33 in CNS Glia
Author(s) -
Hudson Chad A,
Wilmore Joel R,
Christophi George P,
Gruber Ross C,
Massa Paul T
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.2_supplement.432
Subject(s) - arginase , chemokine , cytokine , innate immune system , biology , microbiology and biotechnology , microglia , autocrine signalling , tumor necrosis factor alpha , effector , immunology , immune system , inflammation , chemistry , cell culture , arginine , biochemistry , amino acid , genetics
IL‐33 is a novel member of the IL‐1 cytokine family and is a potent inducer of type 2 immunity as mast cells and Th2 CD4+ T cells respond to IL‐33 with the induction of Th2 cytokines such as IL‐13. IL‐33 mRNA levels are extremely high in the central nervous system (CNS), yet whether IL‐33 is secreted by and affects CNS glia has not been studied. Here, we demonstrate that TLR agonists and IL‐1beta significantly increase IL‐33 mRNA and protein expression in CNS glia. Further, CNS glial cultures treated with IL‐33 were induced to express various innate immune effectors. IL‐33 increased the mRNA levels of the type 2 effector arginase I, the pro‐inflammatory cytokines IL‐6 and TNF‐α and the type 2 chemokines eotaxin‐1 and TARC. Likewise, treatment of glia with IL‐33 induced significant increases in intracellular arginase activity and IL‐6, TNF‐α and MCP‐1 secretion, while the type 1 effector nitric oxide (which has an antagonistic relationship with arginase activity) was not induced. Interestingly, the induction of arginase I was not accompanied by increases in IL‐4 or IL‐13, the two cytokines known to potently induce arginase I transcriptionally. In sum, IL‐33 is highly inducible in CNS glia and once induced, can act in an autocrine manner on the glia to induce Type 2 innate immunity. Hence, the presence of mast cells, Th2 cells and IL‐4/IL‐13 may well not be necessary for the induction Type 2 innate immunity by IL‐33 in the CNS.