2. Academic Validation
  3. Taurohyodeoxycholic acid alleviates trinitrobenzene sulfonic acid induced ulcerative colitis via regulating Th1/Th2 and Th17/Treg cells balance

Taurohyodeoxycholic acid alleviates trinitrobenzene sulfonic acid induced ulcerative colitis via regulating Th1/Th2 and Th17/Treg cells balance

  • Life Sci. 2023 Apr 1:318:121501. doi: 10.1016/j.lfs.2023.121501.
Le Lv 1,  Ziyang Chen 1,  Wenhui Bai 1,  Jiahui Hao 1,  Zhengang Heng 1,  Caijin Meng 1,  Lin Wang 1,  Xianglan Luo 1,  Xinmiao Wang 1,  Yanjun Cao 2,  Jiao He 3
Affiliations

Affiliations

  • 1 Biomedicine Key Laboratory of Shaanxi Province, College of Life Sciences, Northwest University, Xi'an, China.
  • 2 Biomedicine Key Laboratory of Shaanxi Province, College of Life Sciences, Northwest University, Xi'an, China; Key Laboratory of Resource Biology and Biotechnology in Western China (Northwest University), Ministry of Education, Xi'an, China.
  • 3 Biomedicine Key Laboratory of Shaanxi Province, College of Life Sciences, Northwest University, Xi'an, China; Key Laboratory of Resource Biology and Biotechnology in Western China (Northwest University), Ministry of Education, Xi'an, China. Electronic address: hejiao@nwu.edu.cn.
PMID: 36801213 DOI: 10.1016/j.lfs.2023.121501
Abstract

Aims: Taurohyodeoxycholic acid (THDCA), a natural 6α-hydroxylated bile acid, exhibits intestinal anti-inflammatory effects. This study aimed to explore the efficacy of THDCA on ulcerative colitis and to reveal its mechanisms of action.

Main methods: Colitis was induced by intrarectal administration of trinitrobenzene sulfonic acid (TNBS) to mice. Mice in the treatment group were gavage THDCA (20, 40, and 80 mg/kg/day) or sulfasalazine (500 mg/kg/day) or azathioprine (10 mg/kg/day). The pathologic markers of colitis were comprehensively assessed. The levels of Th1-/Th2-/Th17-/Treg-related inflammatory cytokines and transcription factors were detected by ELISA, RT-PCR, and Western blotting. The balance of Th1/Th2 and Th17/Treg cells was analyzed by Flow cytometry.

Key findings: THDCA significantly alleviated colitis by improving the body weight, colon length, spleen weight, histological characteristics, and MPO activity of colitis mice. THDCA reduced the secretion of Th1-/Th17-related cytokines (IFN-γ, IL-12p70, IL-6, IL-17A, IL-21, IL-22, and TNF-α) and the expressions of transcription factors (T-bet, STAT4, RORγt, and STAT3), but increase the production of Th2-/Treg-related cytokines (IL-4, IL-10, and TGF-β1) and the expressions of transcription factors (GATA3, STAT6, Foxp3, and SMAD3) in the colon. Meanwhile, THDCA inhibited the expressions of IFN-γ, IL-17A, T-bet, and RORγt, but improved the expression of IL-4, IL-10, GATA3, and Foxp3 in the spleen. Furthermore, THDCA restored the proportion of Th1, Th2, Th17, and Treg cells, and balanced the Th1/Th2 and Th17/Treg immune response of colitis mice.

Significance: THDCA can alleviate TNBS-induced colitis via regulating Th1/Th2 and Th17/Treg balance, which may represent a promising treatment for patients with colitis.

Keywords

Cytokine; Taurohyodeoxycholic acid; Th1/Th2; Th17/Treg; Ulcerative colitis.

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