Interleukin-25-induced chemokines and interleukin-6 from eosinophils in mediated by p38 mitogen-activated protein kinase, c-jun N-terminal kinase, and nuclear factor-κB

Interleukin (IL)-25, a novel Th2 cytokine, is Capable of amplifying allergic inflammation. We investigated the modulation of nuclear factor (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), 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 enzyme-linked immunosorbent assay. NF-kappa B, c-Jun amino-terminal kinase (INK), and p38 MAPK activities in eosinophils were assessed by electrophoretic mobility shift assay and Western blot. IL-25 was found to upregulate the gene expression of chemokines MCP-1, MIP-1 alpha, and IL-8, and cytokine IL-6, in eosinophils, and to significantly increase the release of the above chemokines and IL-6 from eosinophils. IL-25 could also activate the INK, p38 MAPK, and NF-kappa B activities of eosinophils, while inhibitor of IKB-alpha phosphorylation (BAY11-7082), INK (SP600125), and p38 MAPK (SB203580) could suppress the release of IL-8, MIP-1 alpha, MCPA, and IL-6. Together, the above results showed that the induction of MCPA, MIP-1 alpha, IL-8, and IL-6 in IL-25-activated eosinophils are regulated by INK, p38 MAPK, and NF-kappa B pathways.