Inhibitory effects of glucocorticoids on urocortin-mediated increases in interleukin-6 gene expression in rat aortic smooth muscle cells.
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.
Kageyama
Kazunori
K
Department of Endocrinology, Metabolism and Infectious Diseases, Hirosaki University School of Medicine, 5 Hirosaki, Aomori 036-8562, Japan. kkageyama@hkg.odn.ne.jp
Hanada
Komaki
K
Nigawara
Takeshi
T
Furukawa
Ken-Ichi
K
Terui
Ken
K
Ogura
Eriko
E
Motomura
Shigeru
S
Suda
Toshihiro
T
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
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