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Published ahead of print on April 28, 2005, doi:10.1165/rcmb.2005-0034OC

Am. J. Respir. Cell Mol. Biol., Volume 33, Number 2, August 2005, 186-194

A more recent version of this article appeared on August 1, 2005
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Submitted on January 19, 2005
Revised on April 27, 2005

IL-25 Induced Chemokines and IL-6 Release from Eosinophils is Mediated by p38 MAPK, JNK and NF-{kappa}B

C.K. Wong1, Phyllis F.Y. Cheung1, W.K. Ip1, and Christopher W.K. Lam1*

1 Department of Chemical Pathology, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong

* To whom correspondence should be addressed. E-mail: waikeilam{at}cuhk.edu.hk.

IL-25, a novel Th2 cytokine, is capable of amplifying allergic inflammation. We investigated the modulation of nuclear factor-{kappa}B (NF-{kappa}B) and mitogen-activated protein kinases (MAPK) pathways in IL-25-activated eosinophils, the principal effector cells of allergic inflammation, for the in vitro release of chemokines including monocyte chemoattractant protein-1 (MCP-1), interleukin (IL)-8, and macrophage inflammatory protein (MIP)-1{alpha}, and inflammatory cytokine IL-6. Gene expression of chemokines and IL-6 was evaluated by RT-PCR and concentrations of chemokines and cytokine were measured by cytokine protein array, cytometric bead array and ELISA. NF-{kappa}B, c-Jun amino-terminal kinase (JNK) and p38 MAPK activities in eosinophils were assessed by electrophoretic mobility shift assay and Western blot. IL-25 was found to up-regulate the gene expression of chemokines MCP-1, MIP-1{alpha}, IL-8 and cytokine IL-6 in eosinophils; and significantly increase the release of the above chemokines and IL-6 from eosinophils. IL-25 could also activate the JNK, p38 MAPK and NF-{kappa}B activities of eosinophils, while inhibitor of I{kappa}B-{alpha} phosphorylation (BAY11-7082), JNK (SP600125) and p38 MAPK (SB203580) could suppress the release of IL-8, MIP-1{alpha}, MCP-1 and IL-6. Together, the above results showed that the induction of MCP-1, MIP-1{alpha}, IL-8 and IL-6 in IL-25 activated eosinophils are regulated by JNK, p38 MAPK and NF-{kappa}B pathways.




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