Emodin attenuates adenosine triphosphate‑induced pancreatic ductal cell injury in vitro via the inhibition of the P2X7/NLRP3 signaling pathway

Zhang,Qingkai; Hu,Fenglin; Guo,Fangyue; Zhou,Qi; Xiang,Hong; Shang,Dong

doi:10.3892/or.2019.7270

Emodin attenuates adenosine triphosphate‑induced pancreatic ductal cell injury in vitro via the inhibition of the P2X7/NLRP3 signaling pathway

Authors:
- Qingkai Zhang
- Fenglin Hu
- Fangyue Guo
- Qi Zhou
- Hong Xiang
- Dong Shang
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Affiliations: Department of General Surgery, First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning 116011, P.R. China, Institute (College) of Integrative Medicine, Dalian Medical University, Dalian, Liaoning 116044, P.R. China, Clinical Laboratory of Integrative Medicine, First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning 116011, P.R. China
Published online on: August 8, 2019 https://doi.org/10.3892/or.2019.7270
Pages: 1589-1597

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Abstract

Acute pancreatitis (AP) is an inflammatory disease with high morbidity and mortality rates. Pancreatic ductal cells are the most susceptible of all cell types that are exposed to the noxious stimuli of pancreatitis. Our previous studies demonstrated that emodin, a natural product extracted from Rheum palmatum L., protected pancreatic acinar cells from injutyh due to its anti‑inflammatory activity. In the present study, in order to investigate the protective effects and molecular mechanisms of action of emodin on injured pancreatic ductal cells, an adenosine triphosphate (ATP)‑induced model of cell injury was established using the human pancreatic ductal epithelial cell line, HPDE6‑C7. The results revealed that emodin attenuated ATP‑induced HPDE6‑C7 cell injury by decreasing the levels of inflammatory factors, including interleukin (IL)‑1β and IL‑18. Furthermore, emodin significantly downregulated the protein levels of purinergic receptor P2X, ligand‑gated ion channel, 7 (P2X7), NOD‑like receptor protein 3 (NLRP3), apoptosis‑associated speck‑like protein containing a CARD (ASC) and caspase‑1 in the injured HPDE6‑C7 cells. The results also indicated that emodin attenuated HPDE6‑C7 cell injury at least partially through the inhibition of the P2X7/NLRP3 signaling pathway. The protective effects of emodin were abrogated upon pre‑treatment with P2X7 overexpression plasmid, which further confirmed that the P2X7 signaling pathway is the drug target of the effects of emodin against ATP‑induced pancreatic ductal cell injury. Collectively, the findings of this study demonstrate that emodin attenuates ATP‑induced pancreatic ductal cell injury in AP mainly through the inhibition of the P2X7/NLRP3 signaling pathway. This study suggests that emodin may be further developed for its application in future medical therapy.

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