Interleukin-27 decreases ghrelin production through signal transducer and activator of transcription 3—mechanistic target of rapamycin signaling

Autor: Heng Zhang, Qingjie Li, Yuxin Teng, Yubi Lin, Shaojian Li, Tingfeng Qin, Linxi Chen, Jiana Huang, Hening Zhai, Quan Yu, Geyang Xu
Jazyk: angličtina
Rok vydání: 2020
Předmět:
Zdroj: Acta Pharmaceutica Sinica B, Vol 10, Iss 5, Pp 837-849 (2020)
Druh dokumentu: article
ISSN: 2211-3835
DOI: 10.1016/j.apsb.2019.12.018
Popis: Interleukin-27 (IL-27), a heterodimeric cytokine, plays a protective role in diabetes. Ghrelin, a gastric hormone, provides a hunger signal to the central nervous system to stimulate food intake. The relationship between IL-27 and ghrelin is still unexplored. Here we investigated that signal transducer and activator of transcription 3 (STAT3)—mechanistic target of rapamycin (mTOR) signaling mediates the suppression of ghrelin induced by IL-27. Co-localization of interleukin 27 receptor subunit alpha (WSX-1) and ghrelin was observed in mouse and human gastric mucosa. Intracerebroventricular injection of IL-27 markedly suppressed ghrelin synthesis and secretion while stimulating STAT3–mTOR signaling in both C57BL/6J mice and high-fat diet-induced-obese mice. IL-27 inhibited the production of ghrelin in mHypoE-N42 cells. Inhibition of mTOR activity induced by mTOR siRNA or rapamycin blocked the suppression of ghrelin production induced by IL-27 in mHypoE-N42 cells. Stat 3 siRNA also abolished the inhibitory effect of IL-27 on ghrelin. IL-27 increased the interaction between STAT3 and mTOR in mHypoE-N42 cells. In conclusion, IL-27 suppresses ghrelin production through the STAT3-mTOR dependent mechanism.
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