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Rapamycin Attenuates High Glucose-Induced Inflammation Through Modulation of mTOR/NF-?B Pathways in Macrophages.


ABSTRACT: Background: The NLRP3 inflammasome is one of the key contributors to 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-?B, and NLRP3 inflammasome expression were measured by western blotting. Results: We found that rapamycin reduced NLRP3 inflammasome activation in macrophages. Rapamycin reduced NLRP3 inflammasome activation by inhibiting mTOR phosphorylation and NF-?B activation. Moreover, mTOR siRNA inhibited NF-?B activation, leading to the suppression of NLRP3 inflammasome activation. Conclusion: Rapamycin can ameliorate high glucose-induced NLRP3 inflammasome activation by attenuating the mTOR/NF-?B signaling pathway in macrophages. Rapamycin may act as a possible therapeutic option for high glucose-induced inflammatory response in impaired wound healing in the future.

SUBMITTER: Dai J 

PROVIDER: S-EPMC6831745 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Rapamycin Attenuates High Glucose-Induced Inflammation Through Modulation of mTOR/NF-κB Pathways in Macrophages.

Dai Jiezhi J   Jiang Chaoyin C   Chen Hua H   Chai Yimin Y  

Frontiers in pharmacology 20191030


<b>Background:</b> The NLRP3 inflammasome is one of the key contributors to 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. <b>Methods:</b> 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 NL  ...[more]

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