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IL-22 promotes occludin expression by activating autophagy and treats ulcerative colitis

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Abstract

IL-22 serves a protective function in the intestinal barrier. These protective properties of IL-22 may offer a potential treatment for ulcerative colitis (UC). However, the exact mechanisms of action remain unclear. Autophagy plays an important protective role in stabilizing the intestinal barrier. We aimed to explore the role of autophagy in the IL-22-mediated-protective effects in UC. Dextran sulfate sodium (DSS) was administrated via drinking water over 7 days to induce acute UC in BALB/c mice. Treatments with IL-22 (0.25 μg/10 g bodyweight) were started by intraperitoneal injection on days 1, 3, and 5. Weight, disease activity index, histological score, and myeloperoxidase (MPO) activity were used to evaluate the severity of colitis. The expressions of occludin and autophagy-related proteins LC3BII/I were measured by western blot analysis. The lipopolysaccharide-induced HT-29 cell model was used to explore the mechanism. In vivo, IL-22 significantly alleviated DSS-induced clinical manifestations, reduced histological injury, and inhibited MPO activity. IL-22 upregulated the expression of occludin and the LC3B II/I ratio in the colon. In vitro, IL-22 significantly lowered TNF-α levels and enhanced the expression of occludin and the LC3B II/I ratio. Importantly, inhibiting autophagy in vitro by 3-Methyladenine (3-MA) attenuated the occludin protective effects of IL-22. In summary, our findings demonstrate that IL-22 ameliorates DSS-induced ulcerative colitis, which may be attributable to activating autophagy and then promoting occludin expression.

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Acknowledgements

We thank the cooperation of all participates. This study was supported by grants from the Guangxi Natural Science Foundation Program (2020GXNSFBA159062).

Funding

Funding was supported by Natural Science Foundation of Guangxi Province (Grant Nos. 2020GXNSFBA159062).

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  1. Hui Nong and Haifeng Yuan are joint first author.

Authors and Affiliations

  1. Department of Gastroenterology, Ruikang Hospital Affiliated to Guangxi University of Chinese Medicine, Nanning, 530000, China

    Hui Nong, Haifeng Yuan, Yiting Lin, Siyu Chen, Yanbo Li, Zhaoqiong Luo, Wen Yang, Tao Zhang & Yuanneng Chen

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Contributions

HN and HY performed the main experiments and wrote the manuscript. YL and WY analyzed the raw data. ZL, YL and SC revised the article. YC and TZ designed and conducted the whole work. All authors read and approved the manuscript.

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Correspondence to Tao Zhang or Yuanneng Chen.

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Nong, H., Yuan, H., Lin, Y. et al. IL-22 promotes occludin expression by activating autophagy and treats ulcerative colitis. Mol Cell Biochem (2023). https://doi.org/10.1007/s11010-023-04806-z

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