• Shock · Oct 2018

    Heat Shock Factor 1 Inhibits the Expression of Suppressor of Cytokine Signaling 3 in Cerulein-Induced Acute Pancreatitis.

    • Guiliang Wang, Gui Xiao, Hai Liu, Guangwen Chen, Xiaoli Wang, Ping Wen, Ting Li, Jianbo Wen, and Xianzhong Xiao.
    • Department of Digestive Internal Medicine, Gannan Medical University Pingxiang Hospital, Pingxiang, People's Republic of China.
    • Shock. 2018 Oct 1; 50 (4): 465-471.

    BackgroundHeat shock factor 1 (HSF1), an important transcriptional molecule in the heat shock process, can regulate the expression of a lot of inflammatory mediators in addition to heat shock proteins. This study evaluated the inhibitive function of HSF1 on the expression of suppressor of cytokine signaling 3 in cerulein-induced acute pancreatitis.MethodsAfter HSF1 mice, HSF1 mice, and AR42J cells were treated with cerulein, histopathological score, expression of SOCS3 mRNA, and protein levels were analyzed by using RT-PCR, quantitative real-time RT-PCR, and western blotting, respectively. DNA binding and transcription activity of HSF1 to the SOCS3 promoter were detected by chromatin immunoprecipitation and luciferase reporter assays.ResultsThe histopathological scores of the pancreas decreased significantly in the cerulein-induced HSF1 mice compared with the cerulein-induced HSF1 mice. SOCS3 mRNA and protein level decreased in the pancreas of the unstimulated HSF1 and HSF1 mice, whereas increased in the pancreas of the cerulein-induced HSF1 and HSF1 mice, with higher in the pancreas of cerulein-induced HSF1mice. In the pcDNA3.1-transfected AR42J cells, SOCS3 protein decreased and was upregulated after the cerulein stimulation, whereas HSF1 overexpression inhibited the upregulation. In the scramble-transfected AR42J cells, SOCS3 protein decreased and was upregulated after the cerulein stimulation, whereas HSF1-RNAi further promoted the upregulation. EMSA and chromatin immunoprecipition showed that HSF1 could directly bind to SOCS3 promoter region. Reporter assays showed that HSF1 could inhibit the transcriptional activity on SOCS3 promoter.ConclusionsHSF1 can protect AR42J cells from cerulein-induced pancreatitis through inhibiting the expression of SOCS3.

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