PMID- 20042461 OWN - NLM STAT- MEDLINE DCOM- 20100319 LR - 20191210 IS - 1522-1466 (Electronic) IS - 1522-1466 (Linking) VI - 298 IP - 3 DP - 2010 Mar TI - IL-17A and IL-17F stimulate chemokines via MAPK pathways (ERK1/2 and p38 but not JNK) in mouse cultured mesangial cells: synergy with TNF-alpha and IL-1beta. PG - F779-87 LID - 10.1152/ajprenal.00198.2009 [doi] AB - We investigated the role of IL-17 family members IL-17A and IL-17F in the induction of chemokines in mouse cultured mesangial cells (SV40 MES 13 cells). We evaluated the expression of the chemokines monocyte chemoattractant protein-1 (MCP-1) and macrophage inflammatory protein-2 (MIP-2) by ELISA and real-time RT-PCR (Q-PCR). Activation of MAPK was assessed by immunoblotting. IL-17RA and IL-17RC were inhibited by small interfering RNA (siRNA). We found that IL-17A or IL-17F stimulation of mesangial cells led to both a dose- and time-dependent increase in MCP-1 and MIP-2 release. This effect was dependent on mRNA transcription and protein translation. Both also enhanced TNF-alpha- and IL-1beta-mediated MCP-1 and MIP-2 release in the cells. Additionally, we observed that IL-17A and IL-17F induced MAPK (p38 MAPK, ERK1/2, and JNK) activation and that pharmacological inhibitors of p38 MAPK (SB203580) and ERK1/2 (U0126), but not JNK (SP600125), blocked the IL-17A/IL-17F-mediated MCP-1 and MIP-2 release. Mesangial cells expressed IL-17RA and IL-17RC, and the IL-17A-mediated MCP-1 and MIP-2 release was significantly blocked by soluble IL-17RA. Furthermore, inhibition of either IL-17RA or IL-17RC expression via siRNA led to significant reduction of IL-17A/IL-17F-stimulated chemokine production. We conclude that IL-17A and IL-17F induce the production of chemokines MCP-1 and MIP-2 via MAPK pathways (p38 MAPK and ERK1/2), as well as mRNA transcription and protein translation and have synergistic effects with TNF-alpha and IL-1beta in cultured mesangial cells. FAU - Iyoda, Masayuki AU - Iyoda M AD - Division of Nephrology, Department of Medicine, Showa University School of Medicine, Tokyo, Japan. iyoda@med.showa-u.ac.jp FAU - Shibata, Takanori AU - Shibata T FAU - Kawaguchi, Mio AU - Kawaguchi M FAU - Hizawa, Nobuyuki AU - Hizawa N FAU - Yamaoka, Toshimitsu AU - Yamaoka T FAU - Kokubu, Fumio AU - Kokubu F FAU - Akizawa, Tadao AU - Akizawa T LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20091230 PL - United States TA - Am J Physiol Renal Physiol JT - American journal of physiology. Renal physiology JID - 100901990 RN - 0 (Ccl2 protein, mouse) RN - 0 (Chemokine CCL2) RN - 0 (Chemokine CXCL2) RN - 0 (Chemokines) RN - 0 (Cxcl2 protein, mouse) RN - 0 (Il17a protein, mouse) RN - 0 (Il17f protein, mouse) RN - 0 (Il17ra protein, mouse) RN - 0 (Il17rc protein, mouse) RN - 0 (Interleukin-17) RN - 0 (Interleukin-1beta) RN - 0 (Protein Kinase Inhibitors) RN - 0 (RNA, Messenger) RN - 0 (Receptors, Interleukin) RN - 0 (Receptors, Interleukin-17) RN - 0 (Recombinant Proteins) RN - 0 (Tumor Necrosis Factor-alpha) RN - EC 2.7.11.24 (JNK Mitogen-Activated Protein Kinases) RN - EC 2.7.11.24 (Mitogen-Activated Protein Kinase 1) RN - EC 2.7.11.24 (Mitogen-Activated Protein Kinase 3) RN - EC 2.7.11.24 (Mitogen-Activated Protein Kinases) RN - EC 2.7.11.24 (p38 Mitogen-Activated Protein Kinases) SB - IM MH - Animals MH - Blotting, Western MH - Cell Line MH - Chemokine CCL2/metabolism MH - Chemokine CXCL2/metabolism MH - Chemokines/genetics/*metabolism MH - Enzyme Activation MH - Enzyme-Linked Immunosorbent Assay MH - Humans MH - Interleukin-17/*metabolism MH - Interleukin-1beta/*metabolism MH - JNK Mitogen-Activated Protein Kinases/metabolism MH - Mesangial Cells/drug effects/*enzymology/*immunology MH - Mice MH - Mitogen-Activated Protein Kinase 1/metabolism MH - Mitogen-Activated Protein Kinase 3/metabolism MH - Mitogen-Activated Protein Kinases/antagonists & inhibitors/*metabolism MH - Polymerase Chain Reaction MH - Protein Kinase Inhibitors/pharmacology MH - RNA Interference MH - RNA, Messenger/metabolism MH - Receptors, Interleukin/genetics/metabolism MH - Receptors, Interleukin-17/genetics/metabolism MH - Recombinant Proteins/metabolism MH - Time Factors MH - Transcription, Genetic MH - Tumor Necrosis Factor-alpha/*metabolism MH - Up-Regulation MH - p38 Mitogen-Activated Protein Kinases/metabolism EDAT- 2010/01/01 06:00 MHDA- 2010/03/20 06:00 CRDT- 2010/01/01 06:00 PHST- 2010/01/01 06:00 [entrez] PHST- 2010/01/01 06:00 [pubmed] PHST- 2010/03/20 06:00 [medline] AID - 00198.2009 [pii] AID - 10.1152/ajprenal.00198.2009 [doi] PST - ppublish SO - Am J Physiol Renal Physiol. 2010 Mar;298(3):F779-87. doi: 10.1152/ajprenal.00198.2009. Epub 2009 Dec 30.