期刊名称:Proceedings of the National Academy of Sciences
印刷版ISSN:0027-8424
电子版ISSN:1091-6490
出版年度:2009
卷号:106
期号:14
页码:5954-5959
DOI:10.1073/pnas.0812782106
语种:English
出版社:The National Academy of Sciences of the United States of America
摘要:IL-23/IL-17-induced neutrophil recruitment plays a pivotal role in rheumatoid arthritis (RA). However, the mechanism of the neutrophil recruitment is obscure. Here we report that prostaglandin enhances the IL-23/IL-17-induced neutrophil migration in a murine model of RA by inhibiting IL-12 and IFN {gamma} production. Methylated BSA (mBSA) and IL-23-induced neutrophil migration was inhibited by anti-IL-23 and anti-IL-17 antibodies, COX inhibitors, IL-12, or IFN{gamma} but was enhanced by prostaglandin E2 (PGE2). IL-23-induced IL-17 production was increased by PGE2 and suppressed by COX-inhibition or IL-12. Furthermore, COX inhibition failed to reduce IL-23-induced neutrophil migration in IL-12- or IFN{gamma}-deficient mice. IL-17-induced neutrophil migration was not affected by COX inhibitors, IL-12, or IFN{gamma} but was inhibited by MK886 (a leukotriene synthesis inhibitor), anti-TNF{alpha