Back to Search
Start Over
Peroxisome Proliferator-Activated Receptor Alpha Mediates the Beneficial Effects of Atorvastatin in Experimental Colitis
- Source :
- Frontiers in Immunology, Vol 12 (2021), Frontiers in Immunology, Repositório Institucional da USP (Biblioteca Digital da Produção Intelectual), Universidade de São Paulo (USP), instacron:USP
- Publication Year :
- 2021
- Publisher :
- Frontiers Media S.A., 2021.
-
Abstract
- The current therapeutic options for Inflammatory Bowel Diseases (IBD) are limited. Even using common anti-inflammatory, immunosuppressive or biological therapies, many patients become unresponsive to the treatments, immunosuppressed or unable to restrain secondary infections. Statins are cholesterol-lowering drugs with non-canonical anti-inflammatory properties, whose underlying mechanisms of action still remain poorly understood. Here, we described that in vitro atorvastatin (ATO) treatment was not toxic to splenocytes, constrained cell proliferation and modulated IL-6 and IL-10 production in a dose-dependent manner. Mice exposed to dextran sulfate sodium (DSS) for colitis induction and treated with ATO shifted their immune response from Th17 towards Th2, improved the clinical and histological aspects of intestinal inflammation and reduced the number of circulating leukocytes. Both experimental and in silico analyses revealed that PPAR-α expression is reduced in experimental colitis, which was reversed by ATO treatment. While IBD patients also downregulate PPAR-α expression, the responsiveness to biological therapy relied on the restoration of PPAR-α levels. Indeed, the in vitro and in vivo effects induced by ATO treatment were abrogated in Ppara-/- mice or leukocytes. In conclusion, the beneficial effects of ATO in colitis are dependent on PPAR-α, which could also be a potential predictive biomarker of therapy responsiveness in IBD.
- Subjects :
- Male
Secondary infection
Atorvastatin
Immunology
Peroxisome proliferator-activated receptor
Pharmacology
Inflammatory bowel diseases
statins
Mice
Th2 Cells
Immune system
In vivo
medicine
Animals
Immunology and Allergy
PPAR alpha
INTERLEUCINA 6
Colitis
Original Research
ulcerative colitis
Mice, Knockout
chemistry.chemical_classification
therapy
Interleukin-6
business.industry
Dextran Sulfate
dextran sodium sulfate
RC581-607
medicine.disease
Ulcerative colitis
Interleukin-10
crohn’s disease
chemistry
Th17 Cells
Peroxisome proliferator-activated receptor alpha
Immunologic diseases. Allergy
business
medicine.drug
Subjects
Details
- Language :
- English
- ISSN :
- 16643224
- Volume :
- 12
- Database :
- OpenAIRE
- Journal :
- Frontiers in Immunology
- Accession number :
- edsair.doi.dedup.....13a9f24f27fd89288f3cc7aa310bfa80