Melatonin Induces Anti-Inflammatory Effects to Play a Protective Role via Endoplasmic Reticulum Stress in Acute Pancreatitis

Cell Physiol Biochem. 2016;40(5):1094-1104. doi: 10.1159/000453164. Epub 2016 Dec 14.

Abstract

Background/aims: Melatonin, which is mainly secreted by the pineal gland and released into blood, has anti-inflammatory properties in acute pancreatitis. Many studies show that melatonin can relieve inflammation in taurocholate-induced acute pancreatitis. However, the mechanisms of its anti-inflammatory effects are still undefined, especially the relationship between melatonin and endoplasmic reticulum stress. We explored the anti-inflammatory activity of melatonin in AR42J and rat models.

Methods: The CCK-8 assay was used to assess effects of melatonin on AR42J cell viability. Inflammatory degree and the expressions of endoplasmic reticulum stress related molecules were examined by quantitative RT-PCR and western blotting. The degree of inflammation in the tissue was also accessed by pathological grading. Finally, we used the western blotting method to verify apoptosis and autophagy.

Results: Endoplasmic reticulum stress was obviously activated in early stage inflammation in AR42J and rat models. Melatonin could induce anti-inflammatory effects via endoplasmic reticulum stress. Melatonin significantly inhibited inflammatory cytokines and the expression of ERS-related molecules. Finally, it played a protective role by promoting apoptosis and autophagy of the cells, which were damaged in the process of inflammatory reaction.

Conclusion: Melatonin induces anti-inflammatory effects via endoplasmic reticulum stress in acute pancreatitis to play a protective role.

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / pharmacology*
  • Apoptosis / drug effects
  • Autophagy / drug effects
  • Cell Line
  • Cell Shape / drug effects
  • Cell Survival / drug effects
  • Endoplasmic Reticulum Stress / drug effects*
  • Lipopolysaccharides / pharmacology
  • Male
  • Melatonin / pharmacology*
  • Pancreas / drug effects
  • Pancreas / pathology
  • Pancreatitis / pathology*
  • Protective Agents / pharmacology*
  • Rats, Sprague-Dawley

Substances

  • Anti-Inflammatory Agents
  • Lipopolysaccharides
  • Protective Agents
  • Melatonin