title: Isoform-specific regulation of transforming growth factor-β mRNA expression in macrophages in response to adrenoceptor stimulation.
abstract: Transforming growth factor-beta (TGF-β) is a multifunctional cytokine responsible for both immune regulation and tissue repair. Although TGF-β consists of TGF-β1, -β2, and -β3 in mammals, isoform-selective transcriptional regulation is less well documented in myeloid linage cells such as macrophages. In the present study, the effect of the stress-related catecholamine adrenaline on the expression of TGF-β isoforms in RAW264.7 macrophages and murine bone marrow-derived macrophages was examined. Treatment with adrenaline markedly increased the mRNA expression of TGF-β3 but not of TGF-β1 and -β2. Agonist and antagonist studies indicated that adrenaline-induced TGF-β3 mRNA expression is mediated via β2 -adrenoceptor. Protein kinase A (PKA) inhibitor H89 was found to block an increase in adrenoceptor-mediated TGF-β3 mRNA expression. The membrane-permeable cAMP analog 8-Br-cAMP increased the mRNA expression of TGF-β3 but not of TGF-β1 and -β2. Thus, the β2 -adrenoceptor-mediated cAMP-PKA pathway appears to enhance TGF-β3 mRNA expression in macrophages. Adrenoceptor-mediated TGF-β3 expression by macrophages may influence immune regulation and tissue repair in conditions of stress, during which the sympathetic-nervous system releases catecholamines.
authors.affiliation: Department of Pharmacology, School of Pharmaceutical Sciences, Health Sciences University of Hokkaido, Kanazawa 1757, Ishikari-Tobetsu 061-0293, Japan.
authors.forename: Yoshiki
authors.initials: Y
authors.lastname: Yanagawa
authors.affiliation: Department of Pharmacology, School of Pharmaceutical Sciences, Health Sciences University of Hokkaido, Kanazawa 1757, Ishikari-Tobetsu 061-0293, Japan.
authors.forename: Sachiko
authors.initials: S
authors.lastname: Hiraide
authors.affiliation: Department of Pharmacology, School of Pharmaceutical Sciences, Health Sciences University of Hokkaido, Kanazawa 1757, Ishikari-Tobetsu 061-0293, Japan.
authors.forename: Kenji
authors.initials: K
authors.lastname: Iizuka
mesh_terms: D018674:Adrenergic Antagonists / Q000494:pharmacology*; D000818:Animals; D004837:Epinephrine / Q000494:pharmacology*; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D020033:Protein Isoforms; D000067996:RAW 264.7 Cells; D012333:RNA, Messenger / Q000096:biosynthesis* / Q000235:genetics; D011941:Receptors, Adrenergic / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D016212:Transforming Growth Factor beta / Q000235:genetics* / Q000378:metabolism
chemical_list: D018674:Adrenergic Antagonists; D020033:Protein Isoforms; D012333:RNA, Messenger; D011941:Receptors, Adrenergic; D016212:Transforming Growth Factor beta; D004837:Epinephrine
keywords: adrenaline; macrophages; transforming growth factor; β2-adrenoceptor