Melatonin induces anti-inflammatory effects via endoplasmic reticulum stress in RAW264.7 macrophages

Chen,Yina; Zhao,Qian; Sun,Yangjie; Jin,Yin; Zhang,Jie; Wu,Jiansheng

doi:10.3892/mmr.2018.8613

Melatonin induces anti-inflammatory effects via endoplasmic reticulum stress in RAW264.7 macrophages

Authors:
- Yina Chen
- Qian Zhao
- Yangjie Sun
- Yin Jin
- Jie Zhang
- Jiansheng Wu
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Affiliations: Department of Gastroenterology, Yuyao People's Hospital of Zhejiang, Yuyao, Zhejiang 315400, P.R. China, Department of Gastroenterology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325000, P.R. China, Department of Neurology, Yuyao People's Hospital of Zhejiang, Yuyao, Zhejiang 315400, P.R. China
Published online on: February 15, 2018 https://doi.org/10.3892/mmr.2018.8613
Pages: 6122-6129

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Abstract

Melatonin, which is predominantly secreted by the pineal gland and is released into the blood, appears to have anti‑inflammatory properties. Several studies have shown that melatonin can relieve lipopolysaccharide-induced inflammatory responses of RAW264.7 cells. However, the mechanisms underlying this anti‑inflammatory effect remain to be fully elucidated, particularly the association between melatonin and endoplasmic reticulum (ER) stress (ERS). Therefore, the present study examined the anti‑inflammatory activity of melatonin in RAW264.7 cells and analyzed its molecular mechanisms in ERS. The RAW264.7 cells were stimulated by lipopolysaccharide and treated with melatonin. A Cell Counting Kit‑8 assay was used to assess the toxicity of melatonin. The degree of inflammation was evaluated using ELISA. The expression levels of ERS‑associated protein molecules were examined using reverse transcription‑quantitative polymerase chain reaction and western blot analyses. The results revealed that melatonin had no toxic effect on the RAW264.7 cells at the range of concentrations used in the experiment. Lipopolysaccharide stimulated the cells to produce inflammatory molecules; in the early stage, proteins associated with ERS increased, and then apoptosis occurred. The cells treated with melatonin exhibited attenuated inflammation, decreased expression of ERS‑associated proteins and inhibition of apoptosis. Taken together, the results of the present study showed that melatonin may attenuate the inflammatory response by inhibiting the activation of ERS in RAW264.7 macrophages.

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