NF‑κB regulates HSF1 and c‑Jun activation in heat stress‑induced intestinal epithelial cell apoptosis

Li,Jun; Liu,Yanan; Duan,Pengkai; Yu,Rongguo; Gu,Zhengtao; Li,Li; Liu,Zhifeng; Su,Lei

doi:10.3892/mmr.2017.8199

NF‑κB regulates HSF1 and c‑Jun activation in heat stress‑induced intestinal epithelial cell apoptosis

Authors:
- Jun Li
- Yanan Liu
- Pengkai Duan
- Rongguo Yu
- Zhengtao Gu
- Li Li
- Zhifeng Liu
- Lei Su
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Affiliations: Graduate School, Southern Medical University, Guangzhou, Guangdong 510515, P.R. China, Department of Intensive Care Unit, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong 510515, P.R. China, Department of Intensive Care Unit, Key Laboratory of Tropical Zone Trauma Care and Tissue Repair of PLA, General Hospital of Guangzhou Military Command, Guangzhou, Guangdong 510010, P.R. China, Department of Critical Care Medicine, Fujian Provincial Hospital, Fuzhou, Fujian 350000, P.R. China, Department of Intensive Care Unit, The Third Affiliated Hospital of Southern Medical University, Guangzhou, Guangdong 510630, P.R. China
Published online on: December 6, 2017 https://doi.org/10.3892/mmr.2017.8199
Pages: 3388-3396

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Abstract

Heat stress may induce intestinal epithelial cell apoptosis; however, the molecular mechanisms have not yet been identified. The present study used IEC‑6 rat small intestinal epithelial cells to investigate heat stress‑induced production of reactive oxygen species (ROS), which may be involved in nuclear factor (NF)‑κB activation during heat stress. IEC‑6 cells were transfected with NF‑κB p65‑specific small interfering RNA (siRNA), and observed a significant increase in cell apoptosis and caspase‑3 cleavage; however, in cells transfected with adenovirus that constitutively overexpressed p65, the opposite results were obtained. Furthermore, p65 knockdown increased the heat stress‑induced expression and activity of heat shock transcription factor 1 (HSF1); conversely, p65 overexpression slightly decreased HSF1 activity. The levels of heat stress‑induced c‑Jun phosphorylation were also examined: Knockdown of p65 resulted in a reduction of c‑Jun phosphorylation, whereas p65 overexpression resulted in increased phosphorylation. Furthermore, siRNA‑mediated knockdown of HSF1 in IEC‑6 cells significantly increased heat stress‑induced apoptosis. Cells pretreated with c‑Jun peptide, an inhibitor of c‑Jun activation, exhibited a significant reduction in apoptosis. These findings indicated that heat stress stimulation in IEC‑6 cells induced the pro‑apoptotic role of NF‑κB by regulating HSF1 and c‑Jun activation.

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