Isoform-specific regulation of transforming growth factor-β mRNA expression in macrophages in response to adrenoceptor stimulation

被引:10
|
作者
Yanagawa, Yoshiki [1 ]
Hiraide, Sachiko [1 ]
Iizuka, Kenji [1 ]
机构
[1] Hlth Sci Univ Hokkaido, Sch Pharmaceut Sci, Dept Pharmacol, Kanazawa 1757, Ishikari, Hokkaido 0610293, Japan
基金
日本学术振兴会;
关键词
adrenaline; beta(2)-adrenoceptor; macrophages; transforming growth factor; TGF-BETA; DENDRITIC CELLS; T-CELLS; GROWTH-FACTOR-BETA-1; ACTIVATION; CATECHOLAMINES; NOREPINEPHRINE; TRANSCRIPTION; SELECTIVITY; TGF-BETA-3;
D O I
10.1111/1348-0421.12344
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Transforming growth factor-beta (TGF-beta) is a multifunctional cytokine responsible for both immune regulation and tissue repair. Although TGF-beta consists of TGF-beta 1, -beta 2, and -beta 3 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-beta isoforms in RAW264.7 macrophages and murine bone marrow-derived macrophages was examined. Treatment with adrenaline markedly increased the mRNA expression of TGF-beta 3 but not of TGF-beta 1 and -beta 2. Agonist and antagonist studies indicated that adrenalineinduced TGF-beta 3 mRNA expression is mediated via beta(2)-adrenoceptor. Protein kinase A (PKA) inhibitor H89 was found to block an increase in adrenoceptor-mediated TGF-beta 3 mRNA expression. The membrane-permeable cAMP analog 8-beta r-cAMP increased the mRNA expression of TGF-beta 3 but not of TGF-beta 1 and -beta 2. Thus, the beta(2)-adrenoceptor-mediated cAMP-PKA pathway appears to enhance TGF-beta 3 mRNA expression in macrophages. Adrenoceptor-mediated TGF-beta 3 expression by macrophages may influence immune regulation and tissue repair in conditions of stress, during which the sympathetic-nervous system releases catecholamines.
引用
收藏
页码:56 / 63
页数:8
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