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Immunol Lett. 2017 Apr;184:67-75. doi: 10.1016/j.imlet.2017.02.004. Epub 2017 Feb 22.

IL-17 axis accelerates the inflammatory progression of obese in mice via TBK1 and IKBKE pathway.

Author information

1
The Rheumatism Research Center, Catholic Research Institute of Medical Science, The Catholic University of Korea, Seoul, South Korea. Electronic address: redcap817@catholic.ac.kr.
2
The Rheumatism Research Center, Catholic Research Institute of Medical Science, The Catholic University of Korea, Seoul, South Korea. Electronic address: jhunjy@catholic.ac.kr.
3
The Rheumatism Research Center, Catholic Research Institute of Medical Science, The Catholic University of Korea, Seoul, South Korea. Electronic address: jkbyun0228@catholic.ac.kr.
4
The Rheumatism Research Center, Catholic Research Institute of Medical Science, The Catholic University of Korea, Seoul, South Korea. Electronic address: mnikek@catholic.ac.kr.
5
Impact Biotech, Seoul, 137-040, South Korea. Electronic address: chu4222@catholic.ac.kr.
6
The Catholic University of Korea, School of Medicine, Seoul, 137-040, South Korea. Electronic address: jieunlee@catholic.ac.kr.
7
Division of Hepatology, Department of Internal Medicine, College of Medicine, Seoul St. Mary's Hospital, The Catholic University of Korea, 505 Banpo-Dong, Seocho-Ku, Seoul, 137-040, South Korea. Electronic address: jychoi@catholic.ac.kr.
8
The Rheumatism Research Center, Catholic Research Institute of Medical Science, The Catholic University of Korea, Seoul, South Korea; Division of Rheumatology, Department of Internal Medicine, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, 137-701, South Korea. Electronic address: rapark@catholic.ac.kr.
9
The Rheumatism Research Center, Catholic Research Institute of Medical Science, The Catholic University of Korea, Seoul, South Korea; Division of Rheumatology, Department of Internal Medicine, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, 137-701, South Korea. Electronic address: iammila@catholic.ac.kr.

Abstract

Obesity mediates immune inflammatory response and induces IL-17 expression. Adipgenesis can be regulated by IL-17 and it causes TBK1 activation. The inhibition of TBK1 and the inhibition of I IKBKE reduces inflammatory response and improves obesity. It is hypothesized that IL-17 deficiency inhibits obesity progression and inflammation. 3T3-L1 preadipocytes were differentiated in vitro and treated with IL-17. RAW264.7 cells and differentiated 3T3-L1 were pretreated with TBK1 inhibitor and then stimulated with IL-17. Wild-type and IL-17 knock out mice were fed with high-fat diet. IL-17 inhibits adipocyte differentiation from mouse-derived 3T3-L1 preadipocytes and reduces mRNA expression of proadipogenic transcription factors and adipokines in adipocyte cells. IL-17 also showed up-regulation of mRNA levels of inflammatory cytokines in RAW cells. The inhibitor of TBK1 and IKBKE attenuates the effect of IL-17. Loss of IL-17 deficiency improves diet-induced obesity, fatty liver, glucose and lipid metabolism in mice. The expression of TBK1 and IKBKE decreased in the spleen and liver of IL-17 deficiency mice. Moreover, the inflammatory response within the visceral adipose tissue and Th1 cells were inhibited, however, M2 macrophage and Th2 cells increased in IL-17 deficiency mice. IL-17 inhibits adipogenesis where a lack of IL-17 ameliorates glucose metabolism. As well, the inhibition of TBK1 reduces inflammation induced by IL-17. Therefore, IL-17 may be involved in the development of obesity and metabolic dysfunction in a TBK1-dependent manner.

KEYWORDS:

IL-17; Obesity; TBK1

PMID:
28237848
DOI:
10.1016/j.imlet.2017.02.004
[Indexed for MEDLINE]

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