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

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Abstract

Backround:

Heat shock factor 1 (HSF1), an important transcriptional molecules in the heat shock process, can regulate the expression of a lot of inflammatory mediators in addition to heat shock proteins (HSPs). This study evaluated HSF1 inhibited the expression of suppressor of cytokine signaling 3 in cerulein-induced acute pancreatitis.

Methods:

After HSF1+/+ mice, HSF1-/- mice and AR42J cells were treated with cerulein, histopathological score, expression of SOCS3 mRNA and protein levels were analyzed by uing 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.

Results:

The histopathological scores of the pancreas decreased significantly in the cerulein-induced HSF1+/+ mice compared to the cerulein-induced HSF1-/- mice. SOCS3 mRNA and protein level expressed low in the pancreas of the un-stimulated HSF1-/- mice and HSF1+/+ mice, while increased in the pancreas of the cerulein-induced HSF1-/-mice and HSF1+/+ mice, with higher in the pancreas of cerulein-induced HSF1-/-mice. In the pcDNA3.1 transfected AR42J cells, SOCS3 protein expressed low, and was upregulated after the cerulein stimulation, while HSF1 over-expression inhibited the upregulation. In the scramble transfected AR42J cells, SOCS3 protein expressed low, and was upregulated after the cerulein stimulation, while HSF1-RNAi further promoted the upregulation. EMSA and chromatin immunoprecipition showed that HSF1 can directly bind to SOCS3 promoter region. Reporter assays showed that HSF1 can inhibit the transcriptional activity on SOCS3 promoter.

Conclusion:

HSF1 can protect AR42J cells from cerulein-induced pancreatitis through inhibiting the expression of SOCS3.

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