Interleukin-25-induced chemokines and interleukin-6 release from eosinophils is mediated by p38 mitogen-activated protein kinase, c-Jun N-terminal kinase, and nuclear factor-kappaB.
Interleukin (IL)-25, a novel Th2 cytokine, is capable of amplifying allergic inflammation. We investigated the modulation of nuclear factor (NF)-kappaB 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)-1alpha, 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-kappaB, 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 upregulate the gene expression of chemokines MCP-1, MIP-1alpha, 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 JNK, p38 MAPK, and NF-kappaB activities of eosinophils, while inhibitor of IkappaB-alpha phosphorylation (BAY11-7082), JNK (SP600125), and p38 MAPK (SB203580) could suppress the release of IL-8, MIP-1alpha, MCP-1, and IL-6. Together, the above results showed that the induction of MCP-1, MIP-1alpha, IL-8, and IL-6 in IL-25-activated eosinophils are regulated by JNK, p38 MAPK, and NF-kappaB pathways.
Wong
Chun K
CK
Department of Chemical Pathology, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong.
Cheung
Phyllis F Y
PF
Ip
Wai K
WK
Lam
Christopher W K
CW
D000873:Anthracenes / Q000494:pharmacology; D001483:Base Sequence; D018925:Chemokines / Q000096:biosynthesis* / Q000235:genetics; D018076:DNA, Complementary / Q000235:genetics; D004804:Eosinophils / Q000187:drug effects* / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology; D066298:In Vitro Techniques; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D020381:Interleukin-17; D015850:Interleukin-6 / Q000096:biosynthesis* / Q000235:genetics; D007378:Interleukins / Q000494:pharmacology*; D048031:JNK Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000378:metabolism; D009570:Nitriles / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology; D018123:Receptors, Interleukin / Q000378:metabolism; D011994:Recombinant Proteins / Q000494:pharmacology; D013450:Sulfones / Q000494:pharmacology; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism
C434003:3-(4-methylphenylsulfonyl)-2-propenenitrile; D000873:Anthracenes; D018925:Chemokines; D018076:DNA, Complementary; C486701:IL25 protein, human; D007093:Imidazoles; D020381:Interleukin-17; D015850:Interleukin-6; D007378:Interleukins; D016328:NF-kappa B; D009570:Nitriles; D011725:Pyridines; D018123:Receptors, Interleukin; D011994:Recombinant Proteins; D013450:Sulfones; D018799:Intercellular Adhesion Molecule-1; C432165:pyrazolanthrone; D048031:JNK Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; C093642:SB 203580