ATRA Regulates Innate Immunity in Liver Ischemia/Reperfusion Injury via RARα/Akt/Foxo1 Signaling.

ATRA Regulates Innate Immunity in Liver Ischemia/Reperfusion Injury via RARα/Akt/Foxo1 Signaling.
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ATRA 通过 RARα/Akt/Foxo1 信号传导调节肝脏缺血/再灌注损伤中的先天免疫。

DOI:
10.1248/bpb.b17-00832
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发表时间:
2018-04
期刊:
Biol Pharm Bull
影响因子:
--
通讯作者:
Wang X
Wang X
中科院分区:
其他
文献类型:
--
作者:
Zhong C;Pu L;Fang M;Rao J;Wang X

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All-trans retinoic acid (ATRA) has been proved to protect liver from ischemia/reperfusion (IR) injury, however, its mechanism is still unclear. This study is to investigate the mechanism of effect of ATRA on innate immunity in mice liver IR injury. Before operation, mice were gavaged by ATRA at 15 mg/kg/d for two weeks, and then the liver was underwent 70% ischemia (90 min) and reperfusion (6 h). Liver function was assessed by serum alanine aminotransferase (sALT), serum aspartate aminotransferase (sAST). Real-time PCR and Western blot were to detect the level of mRNA and protein. In vitro, RAW264.7 macrophages were treatment with ATRA (1 µM) or LE540 (5 µM, a retinoic acid receptor α (RARα) receptor antagonist) before lipopolysaccharide (100 ng/mL) stimulation. In vivo, ATRA protected the liver from IR injury by improving hepatocellular function (sALT and sAST), decreasing cell apoptosis and inhibiting inflammatory response (i.e., the level of toll-like receptor 4, transcription factor nuclear factor-κBp65, interleukin (IL)-1β, IL-6, and tumor necrosis factor-α). When RARα was blocked by LE540 in RAW264.7 macrophages, the inflammatory cytokines were enhancing, along with a decline of Akt phosphorylation but Forkhead box o (Foxo) 1, compared with the ATRA group. In summary, ATRA regulates in part the innate immunity to protect liver from IR injury by RARα/Akt/Foxo1 pathway.
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发表时间: 1999-03-19
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