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.
Burýsek
L
L
Institute of Physiology, Academy of Sciences of the Czech Republic, Prague.
Houstek
J
J
D002001:Adipose Tissue, Brown / Q000166:cytology / Q000378:metabolism*; D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000818:Animals; D002478:Cells, Cultured; D003470:Culture Media; D004305:Dose-Response Relationship, Drug; D005786:Gene Expression Regulation; D007375:Interleukin-1 / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D015850:Interleukin-6 / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D051379:Mice; D009638:Norepinephrine / Q000494:pharmacology; D011412:Propanolamines / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D011943:Receptors, Adrenergic, beta / Q000378:metabolism*; D022702:Receptors, Adrenergic, beta-3
D000316:Adrenergic alpha-Agonists; D000318:Adrenergic beta-Agonists; D003470:Culture Media; D007375:Interleukin-1; D015850:Interleukin-6; D011412:Propanolamines; D012333:RNA, Messenger; D011943:Receptors, Adrenergic, beta; D022702:Receptors, Adrenergic, beta-3; C033394:CGP 12177; D009638:Norepinephrine