DPP-IV inhibitor anagliptin exerts anti-inflammatory effects on macrophages, adipocytes, and mouse livers by suppressing NF-κB activation

American Journal of Physiology - Endocrinology and Metabolism - Tập 309 Số 3 - Trang E214-E223 - 2015
Takanori Shinjo1, Yusuke Nakatsu2, Misaki Iwashita1, Tomomi Sano3, Hideyuki Sakoda4, Hideharu Ishihara5, Akifumi Kushiyama6, Midori Fujishiro7, Toshiaki Fukushima1, Yoshihiro Tsuchiya1, Hideaki Kamata1, Fusanori Nishimura1, Tomoichiro Asano2
1Section of Periodontology, Kyushu University Faculty of Dental Science, Fukuoka, Japan
2Department of Medical Chemistry, Division of Molecular Medical Science, Graduate School of Biomedical Sciences, Hiroshima University, Hiroshima, Japan;
3Department of Dental Science for Health Promotion, Division of Cervico-Gnathostomatology, Graduate School of Biomedical Sciences, Hiroshima University, Hiroshima (Japan)
4Department of Internal Medicine, Faculty of Medicine, University of Miyazaki, Miyazaki, Japan
5Division of Diabetes and Metabolic Diseases, Nihon University School of Medicine, Tokyo, Japan
6Division of Diabetes and Metabolism, Institute for Adult Disease, Asahi Life Foundation, Tokyo, Japan; and.
7Department of Internal Medicine, Graduate School of Medicine, University of Tokyo, Tokyo, Japan

Tóm tắt

Dipeptidyl peptidase IV (DPP-IV) expression in visceral adipose tissue is reportedly increased in obese patients, suggesting an association of DPP-IV with inflammation. In this study, first, lipopolysaccharide (LPS)- or palmitate-induced elevations of inflammatory cytokine mRNA expressions in RAW264.7 macrophages were shown to be significantly suppressed by coincubation with a DPP-IV inhibitor, anagliptin (10 μM), despite low DPP-IV expression in the RAW264.7 cells. Regarding the molecular mechanism, LPS-induced degradation of IκBα and phosphorylations of p65, JNK, and p38, as well as NF-κB and AP-1 promoter activities, were revealed to be suppressed by incubation with anagliptin, indicating suppressive effects of anagliptin on both NF-κB and AP-1 signaling pathways. Anagliptin also acted on 3T3-L1 adipocytes, weakly suppressing the inflammatory cytokine expressions induced by LPS and TNFα. When 3T3-L1 and RAW cells were cocultured and stimulated with LPS, the effects of anagliptin on the suppression of cytokine expressions in 3T3-L1 adipocytes were more marked and became evident at the 10 μM concentration. Anti-inflammatory effects of anagliptin were also observed in vivo on the elevated hepatic and adipose expressions and serum concentrations of inflammatory cytokines in association with the suppression of hepatic NF-κB transcriptional activity in LPS-infused mice. Taking these observations together, the anti-inflammatory properties of anagliptin may be beneficial in terms of preventing exacerbation of diabetes and cardiovascular events.

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American Journal of Physiology - Endocrinology and Metabolism

Tập 309 Số 3

E214-E223

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