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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
- Source :
- Molecules, Volume 24, Issue 13, Molecules, Vol 24, Iss 13, p 2475 (2019)
- Publication Year :
- 2019
- Publisher :
- Multidisciplinary Digital Publishing Institute, 2019.
-
Abstract
- Dihydroartemisinin (DHA) is a derivative of the herb Artemisia annua L. that has prominent immunomodulatory activity<br />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.
- 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
Subjects
Details
- Language :
- English
- ISSN :
- 14203049
- Database :
- OpenAIRE
- Journal :
- Molecules
- Accession number :
- edsair.doi.dedup.....1bddba8f34a87b8d31ece02fe1694e29
- Full Text :
- https://doi.org/10.3390/molecules24132475