Interleukin-17A inhibits adipocyte differentiation in human mesenchymal stem cells and regulates pro-inflammatory responses in adipocytes.
The immune system is closely linked to human metabolic diseases. Serum levels of IL-6 increase with obesity and insulin resistance. Not only does IL-6 decrease the insulin sensitivity of human cells such as adipocytes, but it also regulates the lineage commitment of naïve T cells into interleukin (IL)-17A-producing CD4(+) T (Th17) cells. Although IL-17A exerts a variety of effects on somatic tissues, its functional role in human adipocytes has not been identified. In this work, we show that IL-17A inhibits adipocyte differentiation in human bone marrow mesenchymal stem cells (hBM-MSCs), while promoting lipolysis of differentiated adipocytes. We find that IL-17A increases both mRNA and protein secretion of IL-6 and IL-8 during adipocyte differentiation in hBM-MSCs. IL-17A up-regulates cyclooxygenase (COX)-2 gene expression and thereby increases the level of prostaglandin (PG) E(2) in differentiated adipocyes. The suppression of anti-adipogenic PGE(2) by COX inhibitors such as aspirin and NS-398 partially blocked the effect of IL-17A on adipocyte differentiation in hBM-MSCs. Therefore, IL-17A exhibits its inhibitory effect in part via the COX-2 induction in differentiated adipocytes. In addition, treatment with anti-IL-17A antibody neutralizes IL-17A-mediated effects on adipocyte differentiation and function. These results suggest that IL-17A plays a regulatory role in both the metabolic and inflammatory processes of human adipocytes, similar to other pro-inflammatory cytokines such as IL-1, IFNgamma, and TNFalpha.
Shin
Jennifer H
JH
Department of Biology, Bio/Brain Engineering, and Mechanical Engineering, Korea Advanced Institute of Science and Technology, Daejeon, Republic of Korea.
Shin
Dong Wook
DW
Noh
Minsoo
M
D017667:Adipocytes / Q000166:cytology / Q000473:pathology*; D002454:Cell Differentiation; D002478:Cells, Cultured; D051546:Cyclooxygenase 2 / Q000235:genetics; D006801:Humans; D007249:Inflammation; D018836:Inflammation Mediators; D020381:Interleukin-17 / Q000276:immunology / Q000502:physiology*; D015850:Interleukin-6; D016209:Interleukin-8; D008066:Lipolysis; D059630:Mesenchymal Stem Cells / Q000166:cytology*; D015854:Up-Regulation / Q000235:genetics
D018836:Inflammation Mediators; D020381:Interleukin-17; D015850:Interleukin-6; D016209:Interleukin-8; D051546:Cyclooxygenase 2