1. Dihydroartemisinin Regulates the Th/Treg Balance by Inducing Activated CD4+ T cell Apoptosis via Heme Oxygenase-1 Induction in Mouse Models of Inflammatory Bowel Disease
- Author
-
Qi Li, Wei Yan Cai, Si Chao Yan, Ya‑Jie Wang, Yu Jie Li, Ying Chen, Qing Yang, Xiao Xin Zhu, and Xiao Gang Weng
- Subjects
Crohn’s disease ,medicine.medical_treatment ,Pharmaceutical Science ,Dihydroartemisinin ,Apoptosis ,Pharmacology ,Lymphocyte Activation ,T-Lymphocytes, Regulatory ,Inflammatory bowel disease ,Article ,Analytical Chemistry ,Oxazolone ,lcsh:QD241-441 ,Mice ,03 medical and health sciences ,chemistry.chemical_compound ,dihydroartemisinin ,0302 clinical medicine ,lcsh:Organic chemistry ,In vivo ,Drug Discovery ,medicine ,Animals ,Physical and Theoretical Chemistry ,Colitis ,030304 developmental biology ,ulcerative colitis ,0303 health sciences ,Crohn's disease ,Organic Chemistry ,CD4+ T subsets ,heme oxygenase-1 ,T-Lymphocytes, Helper-Inducer ,Inflammatory Bowel Diseases ,medicine.disease ,Artemisinins ,Lymphocyte Subsets ,Heme oxygenase ,Disease Models, Animal ,Trinitrobenzenesulfonic Acid ,chemistry ,Chemistry (miscellaneous) ,Enzyme Induction ,030220 oncology & carcinogenesis ,Molecular Medicine - Abstract
Dihydroartemisinin (DHA) is a derivative of the herb Artemisia annua L. that has prominent immunomodulatory activity, however, its underlying mechanism remains elusive. Inflammatory bowel disease (IBD) is an idiopathic inflammatory condition characterized as an autoimmune disorder that includes dysfunctions in the T helper (Th)/T regulatory cell (Treg) balance, which normally plays pivotal roles in immune homeostasis. The aim of this study was to explore the potential of DHA to ameliorate IBD by restoring the Th/Treg cell balance. To this end, we established mouse models of colitis induced by oxazolone (OXA) and 2,4,6-trinitro-benzene sulfonic acid (TNBS). We then treated mice with DHA at 4, 8, or 16 mg/kg/day. DHA treatment ameliorated colitis signs and reduced lymphocyte infiltration and tissue fibrosis. Moreover, DHA decreased the numbers of Th1 and Th17 cells and Th9 and Th22 cells in TNBS- or OXA-induced colitis, respectively, and increased Tregs in both models. DHA (0.8 mg/mL) also inhibited activated CD4+ T lymphocytes, which was accompanied by apoptosis induction. Moreover, it promoted heme oxygenase-1 (HO-1) production in vitro and in vivo, concomitant with CD4+ T cell apoptosis and restoration of the Th/Treg balance, and these effects were blocked by treatment with the HO-1 inhibitor Sn-protoporphyrin IX. Overall, these results suggest that DHA is a novel and valuable candidate for IBD therapy or Th/Treg immunoregulation.
- Published
- 2019
- Full Text
- View/download PDF