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Melatonin reduces inflammation in intestinal cells, organoids and intestinal explants

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A Correction to this article was published on 08 March 2022

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Abstract

Inflammatory bowel diseases (IBDs) are chronic and recurrent diseases that often occur in young people and place a heavy burden on public health in both developed and developing countries. Melatonin has been confirmed to be useful in various diseases, including Alzheimer’s disease, liver injuries and diseases, and cancers, while its role in IBDs remains unclear. To uncover the function of melatonin in IBDs, three intestinal models, including Caco-2 cells, 3D intestinal organoids and intestinal explants, were used. It was found that different concentrations of melatonin could significantly inhibit the expression levels of NFκB and its downstream cytokines, including IL6 and IL8 in Caco-2 cells (*P < 0.05, **P < 0.01), 3D intestinal organoids (*P < 0.05, **P < 0.01) and intestinal explants (*P < 0.05, **P < 0.01). Melatonin abolished the activation of LPS on the expression levels of NFκB, IL6, and IL8 in three intestinal models (*P < 0.05, **P < 0.01, ***P < 0.001). Importantly, the roles of melatonin in the regulation of inflammation was dependent on its receptor (i.e., MTNR1), since it was found that silencing of the melatonin receptor (MTNR1A) abolished the reduction in inflammation induced by melatonin in Caco-2 cells (***P < 0.001) and 3D intestinal organoids (***P < 0.01, ****P < 0.0001). Herein, the findings in this study might provide useful information for understanding the pathogenesis of IBDs and developing novel drugs to treat the diseases.

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Abbreviations

IBDs:

Inflammatory bowel diseases

3D:

Three dimensional

MTNR:

The melatonin receptor

CD:

Crohn’s disease

UC:

Ulcerative colitis

IL-1β:

Interleukin-1β

LPS:

Lipopolysaccharide

IECM:

Intestinal explant culture medium

EFG:

Epidermal growth factor

SDS:

Sodium dodecyl sulfate

O/N:

Overnight

SD:

Standard deviation

DSS:

Dextran sulfate sodium

AR-V7:

Androgen receptor splice variant-7

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Authors and Affiliations

  1. Anorectal Surgery, Tangshan Gongren Hospital, Tangshan, 063000, Hebei, China

    Xi-Zhang & Xu-ming Zhang

  2. Department of Trauma, Tangshan Gongren Hospital, No. 27, Wenhua Road, Lubei District, Tangshan, 063000, Hebei, China

    Xiao-qiang Yuan

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Contributions

XZ and XM conceived the study. XZ, XY, and XZ designed experiments, and XZ and XZ performed most of the experiments, data collection and data analysis. XZ and XZ wrote the manuscript, which was reviewed by all the authors.

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Correspondence to Xu-ming Zhang.

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The authors have no competing financial interests.

Ethical statement

The animal experiment was performed in strict compliance with the animal experiment guidelines of Tangshan Workers’ Hospital (2020001). The study was approved by the ethics committee of Tangshan Workers’ Hospital (TWH-2020001) for using animals to perform experiments including isolation of cells for the culture of organoids. Informed consent was obtained from the patients, and this study was approved by the ethical committee of Tangshan Workers’ Hospital.

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Xi-Zhang, Yuan, Xq. & Zhang, Xm. Melatonin reduces inflammation in intestinal cells, organoids and intestinal explants. Inflammopharmacol 29, 1555–1564 (2021). https://doi.org/10.1007/s10787-021-00869-w

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  • DOI: https://doi.org/10.1007/s10787-021-00869-w

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