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γ-Glutamylcysteine rescues mice from TNBS-driven inflammatory bowel disease through regulating macrophages polarization

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Abstract

Objective

To explore the molecular mechanism of γ-glutamylcysteine (γ-GC) in response to inflammation in vivo and in vitro on regulating the polarization of macrophages.

Methods

The expressions of gene or protein were assessed by qPCR and Western blot assays, respectively. Cell viability was investigated by CCK-8 assay. Eight-week-old male BALB/c mice were established to examine the therapeutic effects of γ-GC in vivo. The release of TNF-α and IL-4 was determined by ELISA assay. Macrophages polarization was identified by flow cytometry assay.

Results

Our data showed that γ-GC treatment significantly improved the survival, weight loss, and colon tissue damage of IBD mice. Furthermore, we established M1- and M2-polarized macrophages, respectively, and our findings provided evidence that γ-GC switched M1/M2-polarized macrophages through activating AMPK/SIRT1 axis and inhibiting inflammation-related signaling pathway.

Conclusion

Collectively, both in vivo and in vitro experiments suggested that γ-GC has the potential to become a promising novel therapeutic dipeptide for the treatment of IBD, which provide new ideas for the treatment of inflammatory diseases in the future.

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Data availability

No data were used for the research described in the article.

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Acknowledgements

This work was funded by the Natural Science Foundation of China (grant numbers 81771703, 81671565) and the Priority Academic Program Development of Jiangsu Higher Education Institution (PAPD).

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Authors and Affiliations

  1. Jiangsu Province Key Laboratory for Molecular and Medical Biotechnology, College of Life Science, Nanjing Normal University, No. 1 Wenyuan Road, Nanjing, 210046, People’s Republic of China

    Jinyi Zhou, Xintong Yan, Shuai Lu, Xianli Liu, Chen Yang, Yingying Shi & Zhimin Yin

  2. State Key Laboratory of Pharmaceutical Biotechnology, School of Life Science, Nanjing University, Nanjing, 210023, People’s Republic of China

    Lan Luo

  3. Department of Medical Genetics and Cell Biology, School of Basic Medical Sciences, Nanchang University, Nanchang, People’s Republic of China

    Xiaowen Bi

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  1. Jinyi Zhou
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Contributions

ZY, LL, and JZ designed the study. JZ, XY, and XB performed the mouse experiments. JZ, XY, and SL performed the cells experiments. JZ and ZY wrote the manuscript. ZY, LL, JZ, XY, XB, SL, XL, CY, and YS reviewed the manuscript.

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Correspondence to Lan Luo or Zhimin Yin.

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11_2023_1691_MOESM1_ESM.tif

Supplementary file1 Fig.S1 γ-GC regulated macrophages polarization via AMPK/SIRT1 signal pathway (A-H) Raw264.7 cells were stimulated with LPS (100 ng/mL) + IFN-γ (10 ng/mL) or γ-GC (80 μM) in the presence or absence of Compound C (2 μM) or/and EX527 (1 μM), then cell lysates were subjected to immunoblotting using the indicated antibodies. (I, J) Raw264.7 cells were stimulated with IL-4 (20 ng/mL) or γ-GC (80 μM) in the presence or absence of Compound C (2 μM) or/and EX527 (1 μM), then cell lysates were subjected to immunoblotting using the indicated antibodies. Data represent the mean ± SD of at least three independent experiments. **p < 0.01, ***p < 0.001 compared with the LPS+IFN-γ+γ-GC. (TIF 11673 KB)

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Zhou, J., Yan, X., Bi, X. et al. γ-Glutamylcysteine rescues mice from TNBS-driven inflammatory bowel disease through regulating macrophages polarization. Inflamm. Res. 72, 603–621 (2023). https://doi.org/10.1007/s00011-023-01691-6

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