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Role of Janus kinase-2 in IgE receptor-mediated leukotriene C4 production by mast cells



Role of Janus kinase-2 in IgE receptor-mediated leukotriene C4 production by mast cells



Biochemical and Biophysical Research Communications 390(3): 786-790



We have previously shown that Janus kinase 3, a member of the family of non-receptor protein tyrosine kinases, plays a critical role in the regulation of FcepsilonRI-mediated mast cell responses. In the current study, we investigated the role of another JAK family member, JAK2, in these responses. Our results show that the treatment of IgE-sensitized mouse mast cells with an inhibitor of JAK2 (AG490) blocked the release of leukotriene C(4) in a dose-dependent fashion after antigen challenge. However, prostaglandin PG D(2) production and degranulation were not affected under identical experimental conditions. Transfection of RBL-2H3 mast cells with JAK-2 specific small interfering RNA resulted in a 50% reduction of LTC(4) release in response to FcepsilonRI crosslinking, but did not inhibit mast cell degranulation or calcium ionophore-induced LTC(4) release, indicating involvement of JAK2 in IgE receptor-mediated leukotriene release. Taken together, these data suggest that JAK2 is a critical regulator of IgE/antigen-induced production of LTC(4) in mast cells.

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Accession: 055598460

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PMID: 19835845

DOI: 10.1016/j.bbrc.2009.10.050



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