β‐Adrenergic stimulation of interleukin‐1α and interleukin‐6 expression in mouse brown adipocytes

Abstract

Mouse brown adipocytes in primary culture were shown to contain high levels of mRNA for interleukin-la (IL-la) 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-la gene. IL-la 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 ILla and IL-6 genes was stimulated by selective P-adrenergic agonist isoproterenol, p 3 -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 oc-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 Pareceptors 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-la and IL-6 genes in brown adipocytes by catecholamines acting via p 3 -adrenergic receptors. The resulting increase in IL-6 production by brown adipocytes could significantly contribute to systemic levels of IL-6.

Catechol- O -methyltransferase inhibition increases pain sensitivity through activation of both β2- and β3-adrenergic receptors

“…Activation of β 2 ARs on cells in the periphery (Frost et al 2004) or central nervous system (Maimone et al 1993) promotes the synthesis and release of IL-6. Additionally, activation of β 3 ARs on adipocytes stimulates IL-6 transcription (Burysek and Houstek 1997). We have extended these findings in a recent study showing that systemic COMT inhibition increases circulating plasma levels of TNFα, IL-1β, and IL-6 in rat in a β 2 -and β 3 AR-dependent manner (Nackley et al 2005b).…”

“…Within recent years it has become increasingly recognized that proinflammatory mediators, including cytokines (e.g., TNFα, IL-1β, and IL-6), prostaglandins, and reactive oxygen species, also play an important role in mediating pain sensitivity (Burysek and Houstek 1997;Kress 2004;Maimone et al 1993;Marchand et al 2005;Sommer and Kress 2004). Activation of β 2 ARs on cells in the periphery (Frost et al 2004) or central nervous system (Maimone et al 1993) promotes the synthesis and release of IL-6.…”

Vascular Endothelial Growth Factor Is Induced by the Inflammatory Cytokines Interleukin-6 and Oncostatin M in Human Adipose Tissue In Vitro and in Murine Adipose Tissue In Vivo

“…it should be noted that Burysek et al 25 reported an up to 40-fold increase of IL-6 in brown adipocytes stimulated with norepinephrine, a main inducer of thermogenesis. The authors of this article speculated that IL-6 produced by brown adipose tissue could play a paracrine role in the regulation of thermogenesis in this tissue.…”

Cold-Induced Changes in Gene Expression in Brown Adipose Tissue: Implications for the Activation of Thermogenesis

“…In addition to these cells, several tissues including BAT also produce IL-1a. 38) As described above, the receptor of this cytokine exists on the surface of brown adipocytes, and is regulated in response to cold stimulation. 38) In addition, it is also observed that cold stimulation decreases expression of the IL-1a gene.…”

“…The interleukin-1 type I receptor (IL-1RtI) exists on the surface of brown adipocytes. 38) IL1RtI acts as the receptor of interleukin-1a (IL-1a) and IL1b, known as pyrogens secreted from leukocytes. 39) IL1b has the potential to activate thermogenesis.…”