title: Regulation of tristetraprolin expression by mitogen-activated protein kinase phosphatase-1.
abstract: Tristetraprolin (TTP) is an acute phase protein, and its expression is rapidly up-regulated by inflammatory signals, such as lipopolysaccharide (LPS) and cytokines. TTP regulates gene expression by governing the mRNA stability of its target genes, which include cytokines and growth factors. MAP kinase phosphatase-1 (MKP-1) is a nuclear phosphatase that inhibits p38 mitogen-activated protein kinase (MAPK) signaling. This study investigated the role of MKP-1 in TTP expression in A549 human lung epithelial cells, THP-1 human macrophages, J774 mouse macrophages, and primary mouse macrophages. TTP and MKP-1 expression was increased by cytokines or LPS. Silencing of MKP-1 by siRNA enhanced TTP expression in response to LPS, and LPS-induced TTP expression was increased in macrophages from MKP-1 (-/-) mice as compared with that in macrophages from wild-type animals. The inhibition of p38 MAPK by SB202190 reduced TTP expression. In conclusion, MKP-1 suppressed TTP expression by inhibiting p38 MAPK pathway.
authors.affiliation: The Immunopharmacology Research Group, University of Tampere School of Medicine, and Tampere University Hospital, Tampere, Finland.
authors.forename: Noora
authors.initials: N
authors.lastname: Huotari
authors.forename: Tuija
authors.initials: T
authors.lastname: Hömmö
authors.forename: Ville
authors.initials: V
authors.lastname: Taimi
authors.forename: Riina
authors.initials: R
authors.lastname: Nieminen
authors.forename: Eeva
authors.initials: E
authors.lastname: Moilanen
authors.forename: Riku
authors.initials: R
authors.lastname: Korhonen
mesh_terms: D000818:Animals; D002460:Cell Line; D045744:Cell Line, Tumor; D016207:Cytokines / Q000494:pharmacology; D015536:Down-Regulation; D054638:Dual Specificity Phosphatase 1 / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000276:immunology; D020935:MAP Kinase Signaling System / Q000187:drug effects; D008264:Macrophages / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D011725:Pyridines / Q000494:pharmacology; D034622:RNA Interference; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D034741:RNA, Small Interfering; D051816:Tristetraprolin / Q000096:biosynthesis*; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D016207:Cytokines; D007093:Imidazoles; D008070:Lipopolysaccharides; D011725:Pyridines; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D051816:Tristetraprolin; D048051:p38 Mitogen-Activated Protein Kinases; C517019:DUSP1 protein, human; D054638:Dual Specificity Phosphatase 1; C517020:Dusp1 protein, mouse; C090942:4-(4-fluorophenyl)-2-(4-hydroxyphenyl)-5-(4-pyridyl)imidazole