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

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.