PMID- 15860795 OWN - NLM STAT- MEDLINE DCOM- 20050913 LR - 20220316 IS - 1044-1549 (Print) IS - 1044-1549 (Linking) VI - 33 IP - 2 DP - 2005 Aug TI - 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. PG - 186-94 AB - 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. FAU - Wong, Chun K AU - Wong CK AD - Department of Chemical Pathology, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong. FAU - Cheung, Phyllis F Y AU - Cheung PF FAU - Ip, Wai K AU - Ip WK FAU - Lam, Christopher W K AU - Lam CW LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20050428 PL - United States TA - Am J Respir Cell Mol Biol JT - American journal of respiratory cell and molecular biology JID - 8917225 RN - 0 (3-(4-methylphenylsulfonyl)-2-propenenitrile) RN - 0 (Anthracenes) RN - 0 (Chemokines) RN - 0 (DNA, Complementary) RN - 0 (IL25 protein, human) RN - 0 (Imidazoles) RN - 0 (Interleukin-17) RN - 0 (Interleukin-6) RN - 0 (Interleukins) RN - 0 (NF-kappa B) RN - 0 (Nitriles) RN - 0 (Pyridines) RN - 0 (Receptors, Interleukin) RN - 0 (Recombinant Proteins) RN - 0 (Sulfones) RN - 126547-89-5 (Intercellular Adhesion Molecule-1) RN - 1TW30Y2766 (pyrazolanthrone) RN - EC 2.7.11.24 (JNK Mitogen-Activated Protein Kinases) RN - EC 2.7.11.24 (p38 Mitogen-Activated Protein Kinases) RN - OU13V1EYWQ (SB 203580) SB - IM MH - Anthracenes/pharmacology MH - Base Sequence MH - Chemokines/*biosynthesis/genetics MH - DNA, Complementary/genetics MH - Eosinophils/*drug effects/*immunology/metabolism MH - Humans MH - Imidazoles/pharmacology MH - In Vitro Techniques MH - Intercellular Adhesion Molecule-1/metabolism MH - Interleukin-17 MH - Interleukin-6/*biosynthesis/genetics MH - Interleukins/*pharmacology MH - JNK Mitogen-Activated Protein Kinases/antagonists & inhibitors/metabolism MH - NF-kappa B/antagonists & inhibitors/metabolism MH - Nitriles/pharmacology MH - Pyridines/pharmacology MH - Receptors, Interleukin/metabolism MH - Recombinant Proteins/pharmacology MH - Sulfones/pharmacology MH - p38 Mitogen-Activated Protein Kinases/antagonists & inhibitors/metabolism EDAT- 2005/04/30 09:00 MHDA- 2005/09/15 09:00 CRDT- 2005/04/30 09:00 PHST- 2005/04/30 09:00 [pubmed] PHST- 2005/09/15 09:00 [medline] PHST- 2005/04/30 09:00 [entrez] AID - 2005-0034OC [pii] AID - 10.1165/rcmb.2005-0034OC [doi] PST - ppublish SO - Am J Respir Cell Mol Biol. 2005 Aug;33(2):186-94. doi: 10.1165/rcmb.2005-0034OC. Epub 2005 Apr 28.