Melatonin inhibits the endoplasmic reticulum stress‑induced, C/EBP homologous protein‑mediated pathway in acute pancreatitis

Zhao,Qian; Zhang,Hui; Wu,Jie; Lv,Xiangyin; Jin,Xianghong; Hu,Jianwen

doi:10.3892/mmr.2020.11219

Melatonin inhibits the endoplasmic reticulum stress‑induced, C/EBP homologous protein‑mediated pathway in acute pancreatitis

Authors:
- Qian Zhao
- Hui Zhang
- Jie Wu
- Xiangyin Lv
- Xianghong Jin
- Jianwen Hu
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Affiliations: Department of Gastroenterology, Dongyang People's Hospital, Dongyang, Zhejiang 322100, P.R. China, Department of Gastroenterology, Weishan Branch of Dongyang People's Hospital, Dongyang, Zhejiang 322100, P.R. China
Published online on: June 10, 2020 https://doi.org/10.3892/mmr.2020.11219
Pages: 1647-1655

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Abstract

Melatonin, which is mainly secreted by the pineal gland, appears to have anti‑inflammatory activities. Acute pancreatitis (AP) is characterized by inflammation and acinar cell death, and is associated with a high mortality rate. It has been reported that melatonin can alleviate cerulein (Cer) or Cer + lipopolysaccharide (LPS)‑induced inflammatory responses in AR42J rat pancreatic acinar cells (AR42J cells). CCAAT/enhancer binding protein homologous protein (CHOP) is a specific transcription factor involved in endoplasmic reticulum (ER) stress‑induced apoptosis, and regulates ER stress responses. However, the mechanisms of the anti‑inflammatory effects of melatonin' are unknown, particularly the relationship between melatonin and ER stress. Therefore, the present study aimed to investigate the anti‑inflammatory activity of melatonin in AR42J cells and analyze its molecular mechanisms during ER stress. The RNA interference method was used to determine the potential role of CHOP in AR42J cells during AP. In vitro models of AP were induced by treating AR42J cells with Cer + LPS, and pre‑treatment with melatonin was used to identify the potential anti‑inﬂammatory mechanisms. The cells also underwent Cell Counting Kit‑8, western blotting and reverse transcription‑quantitative PCR analyses. The expression levels of ER stress‑related molecules were rapidly activated in the early stage and increased over time in the AR42J AP models, with significant pancreatic inflammation and apoptosis. However, knockdown of CHOP expression significantly reduced apoptosis, the activation of NF‑κB and the downstream signal pathway. Moreover, cells treated with melatonin exhibited attenuated inflammation, decreased expression levels of ER stress‑associated proteins and inhibition of apoptosis. Thus, the present results suggested that melatonin may attenuate the inflammatory response by inhibiting the activation of the CHOP‑mediated pathway in AR42J cells.

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