title: Enhancement of murine serum amyloid A3 mRNA expression by glucocorticoids and its regulation by cytokines.
abstract: Macrophages are regulated by hormones, cytokines, and other substances. We examined the effects of glucocorticoids (GC) on serum amyloid A (SAA) mRNA expression using an antisense SAA3 probe, and found that dexamethasone (DEX) and triamcinolone (TC) increased SAA3 mRNA expression by macrophage cell lines in a time- and concentration-dependent manner. Both an RNA polymerase II antagonist, alpha-amanitin, and a specific GC antagonist, RU38486, inhibited the enhancement of SAA3 mRNA expression by DEX. These results show that GC lead to enhanced SAA3 mRNA transcription. Nuclear run-on experiments supported these results. Enhanced expression of SAA3 mRNA by DEX was accompanied by production of SAA3 protein. Interferon-gamma (IFN-gamma) alone showed any effect on SAA3 mRNA expression. Enhanced SAA3 expression by DEX was inhibited by treatment with IFN-gamma in a dose-dependent manner. Either transforming growth factor (TGF)-beta 1 or interleukin (IL)-4 alone showed no effect on SAA3 mRNA expression, but suppressed DEX-induced SAA3 expression. The timing of the effects of IFN-gamma and TGF-beta 1 on DEX-induced SAA3 expression differed: IFN-gamma showed its effect between 30 h before and 18 h after DEX administration, whereas TGF-beta 1 showed an effect when administered concomitantly with DEX and in the late stages after DEX administration. IL-4 mildly suppressed DEX-induced SAA3 expression when given 12 h before and after DEX administration.
authors.affiliation: Department of Pathology, Oita Medical University, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Ishida
authors.forename: K
authors.initials: K
authors.lastname: Matsuura
authors.forename: M
authors.initials: M
authors.lastname: Setoguchi
authors.forename: Y
authors.initials: Y
authors.lastname: Higuchi
authors.forename: S
authors.initials: S
authors.lastname: Yamamoto
mesh_terms: D000818:Animals; D002460:Cell Line; D016207:Cytokines / Q000494:pharmacology* / Q000502:physiology; D003907:Dexamethasone / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D004347:Drug Interactions; D015870:Gene Expression / Q000187:drug effects; D015847:Interleukin-4 / Q000494:pharmacology; D008264:Macrophages / Q000378:metabolism / Q000502:physiology; D051379:Mice; D015735:Mifepristone / Q000494:pharmacology; D012333:RNA, Messenger / Q000187:drug effects / Q000235:genetics* / Q000378:metabolism; D000685:Serum Amyloid A Protein / Q000187:drug effects* / Q000235:genetics*; D016212:Transforming Growth Factor beta / Q000494:pharmacology
chemical_list: D016207:Cytokines; D012333:RNA, Messenger; C076498:Saa3 protein, mouse; D000685:Serum Amyloid A Protein; D016212:Transforming Growth Factor beta; D015847:Interleukin-4; D015735:Mifepristone; D003907:Dexamethasone