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

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.

• Authors: Le Lv, Ziyang Chen, Wenhui Bai, Jiahui Hao, Zhengang Heng, Caijin Meng, Lin Wang, Xianglan Luo, Xinmiao Wang, Yanjun Cao, Jiao He
• Journal: Life sciences (Life Sci) Vol. 318 Pg. 121501 (Apr 01 2023) ISSN: 1879-0631 [Electronic] Netherlands
• PMID: 36801213 (Publication Type: Journal Article)
• Copyright: Copyright © 2023 Elsevier Inc. All rights reserved.

Chemical References

• Interleukin-17
• Interleukin-10
• taurohyodeoxycholic acid
• Nuclear Receptor Subfamily 1, Group F, Member 3
• Trinitrobenzenesulfonic Acid
• Interleukin-4
• Cytokines
• Forkhead Transcription Factors

Topics

• Mice
• Animals
• Colitis, Ulcerative (pathology)
• T-Lymphocytes, Regulatory
• Interleukin-17
• Interleukin-10
• Nuclear Receptor Subfamily 1, Group F, Member 3
• Trinitrobenzenesulfonic Acid
• Interleukin-4 (pharmacology)
• Colitis (chemically induced)
• Cytokines (metabolism)
• Forkhead Transcription Factors (metabolism)
• Th17 Cells