Role of Janus kinase-2 in IgE receptor-mediated leukotriene C4 production by mast cells.
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.
Sur
Runa
R
Johnson and Johnson Consumer and Personal Products Worldwide, Skillman, NJ 19477-0776, USA.
Hall
Jeffrey
J
Cavender
Druie
D
Malaviya
Ravi
R
D000818:Animals; D002478:Cells, Cultured; D053614:Janus Kinase 2 / Q000235:genetics / Q000378:metabolism*; D017997:Leukotriene C4 / Q000096:biosynthesis*; D008407:Mast Cells / Q000201:enzymology*; D051379:Mice; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D034741:RNA, Small Interfering / Q000235:genetics; D017455:Receptors, IgE / Q000378:metabolism*; D020032:Tyrphostins / Q000494:pharmacology
D047428:Protein Kinase Inhibitors; D034741:RNA, Small Interfering; D017455:Receptors, IgE; D020032:Tyrphostins; C095512:alpha-cyano-(3,4-dihydroxy)-N-benzylcinnamide; D017997:Leukotriene C4; D053614:Janus Kinase 2