3, 3′-diindolylmethane alleviates steatosis and the progression of NASH partly through shifting the imbalance of Treg/Th17 cells to Treg dominance
| Autor: | Fu-ping Wang, Wei Jiang, Jing Li, Ji-Yao Wang, Yun Liu, Wei-min She |
|---|---|
| Rok vydání: | 2014 |
| Předmět: |
CD4-Positive T-Lymphocytes
3 3'-Diindolylmethane Indoles genetic structures Immunology Diindolylmethane chemical and pharmacologic phenomena Inflammation T-Lymphocytes Regulatory Choline Mice chemistry.chemical_compound Methionine Non-alcoholic Fatty Liver Disease medicine Animals Immunology and Allergy IL-2 receptor Cells Cultured Pharmacology biology FOXP3 hemic and immune systems Aryl hydrocarbon receptor medicine.disease Diet Mice Inbred C57BL Toll-Like Receptor 4 Liver chemistry TLR4 biology.protein Th17 Cells Female sense organs medicine.symptom Steatosis Spleen |
| Zdroj: | International Immunopharmacology. 23:489-498 |
| ISSN: | 1567-5769 |
| Popis: | This study was designed to discuss the effects of 3, 3'-diindolylmethane (DIM) on methionine-choline-deficient (MCD)-diet induced mouse nonalcoholic steatohepatitis (NASH) and the potential mechanisms. NASH mice were administrated with or without DIM at different concentrations for 8 weeks. Both the in-vivo and in-vitro effects of DIM on Treg/Th17 imbalance during NASH progression were analyzed. The in-vivo blocking of CD25 or IL-17 was performed to respectively deplete respective function of Treg or Th17 subset. Besides, with the assistance of AhR antagonist CH223191 and anti-TLR4 neutralizing antibody, we designed the in-vitro DIM-incubation experiments to discuss the roles of aryl hydrocarbon receptor (AhR) (CYP1A1, CYP1B1) and toll-like receptor 4 (TLR4) on DIM's effects when shifting Treg/Th17 imbalance. Notably, in NASH mouse models, DIM alleviated hepatic steatosis and inflammation, and shifted the Treg/Th17 imbalance from MCD diet-induced Th17 dominance to Treg dominance. In-vitro, DIM not only significantly up-regulated the mRNAs of Foxp3 (Treg-specific) in purified spleen CD4(+) T cells, but also enhanced the immunosuppressive function of these Treg cells. Besides, DIM significantly up-regulated the proteins of CYP1A1 and CYP1B1 whereas down-regulated those of TLR4 on CD4(+) T cells from MCD-diet mice. Moreover, blocking AhR attenuated while blocking TLR4 enhanced the effects of DIM when regulating Treg/Th17 imbalance. Conclusively, DIM could be used as a potential therapeutic candidate to treat NASH based on its dramatic induction of Treg dominance to alleviate intra-hepatic inflammation, suggesting us a clue that the dietary cruciferous vegetables (containing abundant DIM) might exist as a protective factor for patients with NASH-related liver diseases. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full Text from ScienceDirect