Open AccessSuppression of TLR 4 by miR‐448 is involved in Diabetic development via regulating Macrophage polarization
Author(s) -
Zhao Qing,
Wang Xin,
Hu Qiaosheng,
Zhang Ridong,
Yin Yong
Publication year - 2019
Publication title -
journal of pharmacy and pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.745
H-Index - 118
eISSN - 2042-7158
pISSN - 0022-3573
DOI - 10.1111/jphp.13048
Subject(s) - tlr4 , macrophage polarization , polarization (electrochemistry) , macrophage , diabetes mellitus , medicine , endocrinology , chemistry , microbiology and biotechnology , biology , biochemistry , inflammation , in vitro
Objectives Lipopolysaccharide ( LPS ) contributed to the development and progression of type 2 diabetes mellitus (T2D), while TLR 4 is reported to mediate the LPS ‐induced inflammation in macrophages. However, the potential molecular mechanisms for TLR 4‐mediated macrophages activation in T2D have not yet to be fully clarified. Methods Type 2 diabetes models in C57 BL /6J mice were generated by a combination administration of streptozotocin ( STZ ) and a high‐fat diet ( HFD ). Cell proportions of M1 and M2 macrophages were analyzed using flow cytometry. Expression profiles of miR‐448 and TLR 4 were determined by qRT ‐ PCR and Western blot. Key findings LPS / IFN ‐γ significantly induced M1 polarization in macrophages characterized by the increased levels of TNF ‐α, IL ‐6, IL ‐12, iNOS and decreased levels of TNF ‐β, CCL ‐22, IL ‐10 and Arg‐1, with a higher expression of toll‐like receptor 4 ( TLR 4) in vitro . Consistently, T2 D mice‐derived macrophages had a significantly elevated expression of TLR 4 mRNA and decreased expression of miR‐448. We further confirmed that miR‐448 could inhibit TLR 4 expression by targeting the 3′‐ UTR of TLR 4, rescuing the LPS / IFN ‐γ‐induced M1 macrophage polarization. Conclusions Taken together, our results indicated that decreased miR‐448 in diabetic macrophages may contribute to LPS ‐induced M1 polarization by targeting TLR 4, thereby modulating T2 D development.