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

  • Inflamm Res. 2023 Mar;72(3):603-621. doi: 10.1007/s00011-023-01691-6.
Jinyi Zhou  1 ,  Xintong Yan  1 ,  Xiaowen Bi  2 ,  Shuai Lu  1 ,  Xianli Liu  1 ,  Chen Yang  1 ,  Yingying Shi  1 ,  Lan Luo  3 ,  Zhimin Yin  4
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.
  • 2. Department of Medical Genetics and Cell Biology, School of Basic Medical Sciences, Nanchang University, Nanchang, People's Republic of China.
  • 3. State Key Laboratory of Pharmaceutical Biotechnology, School of Life Science, Nanjing University, Nanjing, 210023, People's Republic of China. [email protected].
  • 4. 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. [email protected].
PMID: 36690783 DOI: 10.1007/s00011-023-01691-6
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.

Keywords
AMPK; Inflammatory bowel disease; Macrophages polarization; SIRT1; γ-Glutamylcysteine.
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