GSK3β inhibition attenuates LPS-induced IL-6 expression in porcine adipocytes

作者：Wang, Linjie; Li, Xueying; Wang, Yan^*

来源：Scientific Reports, 2018, 8(1): 15967.

DOI：10.1038/s41598-018-34186-0

• GLYCOGEN-SYNTHASE KINASE-3
• NF-KAPPA-B
• INSULIN-RESISTANCE
• INTERLEUKIN-6
• GSK3
• INFLAMMATION
• PHOSPHORYLATION
• PROTEINS
• PROMOTER
• CELLS

IL-6 is not only a proinflammatory cytokine associated with inflammatory responses but also a regulator on the energy and glucose metabolism in adipose tissue. Glycogen synthase kinase 3 beta (GSK3 beta) has fundamental roles in the regulation of pro- and anti-inflammatory cytokines production. However, the regulatory role for GSK3 beta in the pig inflammatory response in adipocytes remains unknown. We show here that SB216763 and LPS increased the phosphorylation of GSK3 beta (Ser9), and decreased the phosphorylation of GS (Ser641) in adipocytes. The activity of porcine GSK3 beta was inhibited by SB216763, an inhibitor of GSK3 beta, attenuated the production of IL-6 in LPS-stimulated adipocytes. Additionally, the essential core region of the pig IL-6 promoter located at -191 bp to -59 bp, and an NF-kappa Bp65 element in this region was responsible for IL-6 promoter activity. The transcription activity of NF-kappa Bp65 was activated by LPS stimulation, and the GSK3 beta inhibition repressed LPS-induced luciferase activity of the IL-6 promoter. Furthermore, LPS increased p65 binding to the NF-kappa B site, and GSK3 beta inhibition had no effect on the association of NF-kappa Bp65 with IL-6 gene promoter after LPS treatment. These results demonstrate that GSK3 beta has important regulatory roles in the LPS-induced inflammatory response of IL-6 production in pig adipocytes.

• 出版日期2018-10-29
• 单位四川农业大学