title: Regulation of Inflammatory Cytokine Production by MKP-5 in Macrophages.
abstract: Mitogen-activated protein kinases (MAPKs) include p38 MAPKs, c-Jun N-terminal kinases (JNKs) and Extracellular signal-regulated kinases (ERKs), and they regulate many cell processes, such as cell division, differentiation and release of inflammatory mediators. MAPK activity is controlled by mitogen-activated protein kinase phosphatases (MKPs), a phosphatase family with 11 members. MKP-1 is the most studied member of MKP family, and it is one of the anti-inflammatory factors induced by glucocorticoids. Less is known about the other MAPK phosphatases although they hold a promise as anti-inflammatory drug targets. In this study, we investigated the effect of MKP-5 on MAPK phosphorylation and cytokine production in J774 mouse macrophages. We used MKP-5 siRNA and an MKP-5 inhibitor (AS077234-4) to modulate MKP-5 function. We found that MKP-5 controlled p38 MAPK phosphorylation, but not that of JNK or ERK. In addition, the production of IL-6 and TNF was suppressed by MKP-5 in macrophages. Our results introduce a novel concept that compounds able to enhance MKP-5 expression and/or activity hold anti-inflammatory potential, because MKP-5 down-regulates the release of inflammatory mediators by controlling p38 MAPK activity.
authors.affiliation: The Immunopharmacology Research Group, University of Tampere School of Medicine and Tampere University Hospital, Tampere, Finland.
authors.forename: Tuija
authors.initials: T
authors.lastname: Hömmö
authors.affiliation: Immunoregulation, BioMediTech, University of Tampere, Tampere, Finland.|Department of Dermatology and Fimlab Laboratories, Pirkanmaa Hospital District, Tampere, Finland.
authors.forename: Marko
authors.initials: M
authors.lastname: Pesu
authors.affiliation: The Immunopharmacology Research Group, University of Tampere School of Medicine and Tampere University Hospital, Tampere, Finland.
authors.forename: Eeva
authors.initials: E
authors.lastname: Moilanen
authors.affiliation: The Immunopharmacology Research Group, University of Tampere School of Medicine and Tampere University Hospital, Tampere, Finland.
authors.forename: Riku
authors.initials: R
authors.lastname: Korhonen
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism*; D015536:Down-Regulation / Q000502:physiology; D054637:Dual-Specificity Phosphatases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D018836:Inflammation Mediators / Q000378:metabolism*; D008264:Macrophages / Q000378:metabolism*; D051379:Mice; D010766:Phosphorylation / Q000502:physiology; D034741:RNA, Small Interfering / Q000008:administration & dosage; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D016207:Cytokines; D018836:Inflammation Mediators; D034741:RNA, Small Interfering; D048051:p38 Mitogen-Activated Protein Kinases; C505617:Dusp10 protein, mouse; D054637:Dual-Specificity Phosphatases