beta-Adrenergic stimulation of interleukin-1alpha and interleukin-6 expression in mouse brown adipocytes

Mouse brown adipocytes in primary culture were shown to contain high levels of mRNA for interleukin-1alpha (IL-1alpha) which could be further stimulated up to 9-fold by norepinephrine (NE). Even higher stimulation by NE, up to 40-fold, was found in case of interleukin-6 (IL-6). Time-course of activation of both genes was biphasic, but the response of IL-6 gene was slower than of IL-1alpha gene. IL-1alpha mRNA level reached the maximum after 1 h and the second, lower increase, occurred after 8 h. IL-6 mRNA level showed first maximum after 2 h, but the highest level was found after 8 h. Similarly to NE, the expression of IL-1alpha and IL-6 genes was stimulated by selective beta-adrenergic agonist isoproterenol, beta3-selective agonist CGP-12117, forskoline and db-cAMP. The activation of both genes by CGP-12177 was dose-dependent with the optimum at 100 nM concentration. Stimulation of alpha-adrenergic receptors by cirazoline and oxymetazoline was without any effect. When the expression of IL-6 was studied at the protein level, the stimulation of IL-6 gene via beta3-receptors resulted in secretion of IL-6 up to the concentration 10 ng/ml culture media in 24 h. The results indicate a new type of regulation of expression of IL-1alpha and IL-6 genes in brown adipocytes by catecholamines acting via beta3-adrenergic receptors. The resulting increase in IL-6 production by brown adipocytes could significantly contribute to systemic levels of IL-6.