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Original Research ARTICLE Provisionally accepted The full-text will be published soon. Notify me

Front. Pharmacol. | doi: 10.3389/fphar.2019.01292

Rapamycin attenuates high glucose-induced inflammation through modulation of mTOR/ NF-κB pathways in macrophages

Jiezhi Dai1, Chaoyin Jiang2,  Hua Chen3* and Yimin Chai1
  • 1Department of Orthopedics, Shanghai Sixth People’s Hospital, China
  • 2Department of Orthopaedic Surgery, Shanghai Sixth People's Hospital, China
  • 3Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Department of Orthopedics, Shanghai Sixth People’s Hospital, China

Background: NLRP3 inflammasome is one of the key contributors to the impaired wound healing in diabetes. In this study, we assessed the role of rapamycin on high glucose-induced inflammation in THP-1-derived macrophages and investigated the underlying signaling mechanisms.
Methods: THP-1-derived macrophages were treated with high glucose to induce NLRP3 inflammasome activation. The cells were pretreated with rapamycin, BAY 11-7082 or PDTC before exposure to HG. mTOR, NF-κB and NLRP3 inflammasome expression were measured by western blot.
Results: In our experiment, we found rapamycin reduces NLRP3 inflammasome activation in macrophages. Rapamycin reduced NLRP3 inflammasome activation by inhibiting mTOR phosphorylation and NF-κB activation. Moreover, mTOR siRNA inhibited NF-κB activation, leading to the suppression of NLRP3 inflammasome activation.
Conclusion: Rapamycin could ameliorate high glucose-induced NLRP3 inflammasome activation by attenuating the mTOR/NF-κB signaling pathway in macrophages. Rapamycin might act as a possible therapeutic option for high glucose-induced inflammatory response in impaired wound healing in the future.

Keywords: diabetic wound, NLRP3 inflammasome, mTOR, NF-κB, rapamycin

Received: 15 Jun 2019; Accepted: 09 Oct 2019.

Copyright: © 2019 Dai, Jiang, Chen and Chai. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Dr. Hua Chen, Department of Orthopedics, Shanghai Sixth People’s Hospital, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China, chuadr@aliyun.com