title: Inhibitory effects of glucocorticoids on urocortin-mediated increases in interleukin-6 gene expression in rat aortic smooth muscle cells.
abstract: Urocortin (Ucn) 1, Ucn2, and Ucn3 have potent effects on appetite and the cardiovascular system. Endogenous Ucns in combination with CRF receptor type 2beta may have a physiological role in the cardiovascular system. We previously demonstrated that both Ucn1 and Ucn2 increased IL-6 output levels in A7r5 aortic smooth muscle cells. In the present study, we extended observations on stress or hormone-induced changes in IL-6 gene expression in the cardiovascular system, and determined the effects of glucocorticoids on Ucn-mediated increases in IL-6 mRNA levels, protein levels, and gene transcription activity in A7r5 cells. Ucn1, Ucn2, and Ucn3 all increased IL-6 mRNA levels via CRF receptor type 2. Dexamethasone blocked the ability of Ucn1 to increase IL-6 mRNA and protein levels, while it failed to attenuate the Ucns-mediated changes in cyclic AMP (cAMP)-response element binding protein or extracellular signal-related kinases phosphorylation. Dexamethasone also suppressed Ucn1- or cAMP-stimulated IL-6 gene transcription via a glucocorticoid receptor. Together, these findings demonstrate that glucocorticoids suppress IL-6 gene transcription via Ucn-induced cAMP-dependent pathways in A7r5 cells.
authors.affiliation: Department of Endocrinology, Metabolism and Infectious Diseases, Hirosaki University School of Medicine, 5 Hirosaki, Aomori 036-8562, Japan. kkageyama@hkg.odn.ne.jp
authors.forename: Kazunori
authors.initials: K
authors.lastname: Kageyama
authors.forename: Komaki
authors.initials: K
authors.lastname: Hanada
authors.forename: Takeshi
authors.initials: T
authors.lastname: Nigawara
authors.forename: Ken-Ichi
authors.initials: K
authors.lastname: Furukawa
authors.forename: Ken
authors.initials: K
authors.lastname: Terui
authors.forename: Eriko
authors.initials: E
authors.lastname: Ogura
authors.forename: Shigeru
authors.initials: S
authors.lastname: Motomura
authors.forename: Toshihiro
authors.initials: T
authors.lastname: Suda
mesh_terms: D000818:Animals; D001011:Aorta / Q000166:cytology; D015153:Blotting, Western; D002460:Cell Line; D003346:Corticotropin-Releasing Hormone / Q000494:pharmacology*; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism; D003907:Dexamethasone / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D015870:Gene Expression / Q000187:drug effects*; D005938:Glucocorticoids / Q000494:pharmacology*; D006801:Humans; D015850:Interleukin-6 / Q000235:genetics*; D051379:Mice; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D032389:Myocytes, Smooth Muscle / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D051381:Rats; D018019:Receptors, Corticotropin-Releasing Hormone / Q000037:antagonists & inhibitors / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013997:Time Factors; D014158:Transcription, Genetic / Q000187:drug effects; D054832:Urocortins
chemical_list: D017362:Cyclic AMP Response Element-Binding Protein; D005938:Glucocorticoids; D015850:Interleukin-6; D018019:Receptors, Corticotropin-Releasing Hormone; C426704:UCN3 protein, human; D054832:Urocortins; D003907:Dexamethasone; D003346:Corticotropin-Releasing Hormone; D048049:Extracellular Signal-Regulated MAP Kinases