title: Suppression of cytokine production by glucocorticoids is mediated by MKP-1 in human lung epithelial cells.
abstract: Mitogen-activated protein kinase phosphatase 1 (MKP-1) expression is induced by inflammatory factors and serves as an endogenous p38 MAPK suppressor to limit inflammatory response. Glucocorticoids are very effective anti-inflammatory drugs and they are used for the treatment of many inflammatory diseases, such as asthma and COPD. We investigated the role of MKP-1 in the inhibition of cytokine production by dexamethasone in human A549 bronchial epithelial cells. We found that dexamethasone increased MKP-1 expression, inhibited p38 MAPK phosphorylation, and suppressed TNF and MIP-3α production in A549 cells. Interestingly, the suppression of p38 MAPK phosphorylation and the inhibition of TNF expression by dexamethasone were attenuated in cells, where MKP-1 expression was silenced by siRNA. In conclusion, these data suggest that dexamethasone increases MKP-1 expression and this results in the suppression of p38 MAPK signaling leading to the inhibition of cytokine production in human bronchial epithelial cells. These results point to the role of MKP-1 as an important factor in the therapeutic effects of glucocorticoids in the treatment of inflammatory lung diseases.
authors.affiliation: The Immunopharmacology Research Group, University of Tampere School of Medicine, and Tampere University Hospital, University of Tampere, FI-33014, Tampere, Finland.
authors.forename: Tiina
authors.initials: T
authors.lastname: Keränen
authors.affiliation: The Immunopharmacology Research Group, University of Tampere School of Medicine, and Tampere University Hospital, University of Tampere, FI-33014, 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, University of Tampere, FI-33014, Tampere, Finland. riku.korhonen@staff.uta.fi.
authors.forename: Riku
authors.initials: R
authors.lastname: Korhonen
mesh_terms: D000072283:A549 Cells; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D016207:Cytokines / Q000378:metabolism; D003907:Dexamethasone / Q000494:pharmacology*; D015536:Down-Regulation; D054638:Dual Specificity Phosphatase 1 / Q000235:genetics / Q000378:metabolism*; D004847:Epithelial Cells / Q000187:drug effects* / Q000378:metabolism; D005938:Glucocorticoids / Q000494:pharmacology*; D006801:Humans; D008168:Lung / Q000166:cytology; D010766:Phosphorylation / Q000187:drug effects; D012333:RNA, Messenger / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D000893:Anti-Inflammatory Agents; D016207:Cytokines; D005938:Glucocorticoids; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D003907:Dexamethasone; D048051:p38 Mitogen-Activated Protein Kinases; C517019:DUSP1 protein, human; D054638:Dual Specificity Phosphatase 1
keywords: Cytokine; DUSP1; Inflammation; MKP-1