T cell PPARγ is required for the anti-inflammatory efficacy of abscisic acid against experimental IBD
| Autor: | Josep Bassaganya-Riera, Nicholas P. Evans, Raquel Hontecillas, Amir J. Guri |
|---|---|
| Rok vydání: | 2011 |
| Předmět: |
medicine.drug_class
Endocrinology Diabetes and Metabolism T cell Clinical Biochemistry Anti-Inflammatory Agents Down-Regulation Peroxisome proliferator-activated receptor Mice Transgenic Inflammation Pharmacology Biology T-Lymphocytes Regulatory Biochemistry Inflammatory bowel disease Article Anti-inflammatory Flow cytometry Animals Genetically Modified Mice 03 medical and health sciences 0302 clinical medicine medicine Animals Mesenteric lymph nodes Receptor Molecular Biology 030304 developmental biology chemistry.chemical_classification 0303 health sciences Nutrition and Dietetics medicine.diagnostic_test Inflammatory Bowel Diseases medicine.disease 3. Good health PPAR gamma medicine.anatomical_structure chemistry 030220 oncology & carcinogenesis Immunology medicine.symptom Abscisic Acid |
| Zdroj: | The Journal of Nutritional Biochemistry. 22:812-819 |
| ISSN: | 0955-2863 |
| DOI: | 10.1016/j.jnutbio.2010.06.011 |
| Popis: | The phytohormone abscisic acid (ABA) has been shown to be effective in ameliorating chronic and acute inflammation. The objective of this study was to investigate whether ABA's anti-inflammatory efficacy in the gut is dependent on peroxisome proliferator-activated receptor γ (PPARγ) in T cells. PPARγ-expressing and T cell-specific PPARγ null mice were fed diets with or without ABA (100 mg/kg) for 35 days prior to challenge with 2.5% dextran sodium sulfate. The severity of clinical disease was assessed daily, and mice were euthanized on Day 7 of the dextran sodium sulfate challenge. Colonic inflammation was assessed through macroscopic and histopathological examination of inflammatory lesions and real-time quantitative RT-PCR-based quantification of inflammatory genes. Flow cytometry was used to phenotypically characterize leukocyte populations in the blood and mesenteric lymph nodes. Colonic sections were stained immunohistochemically to determine the effect of ABA on colonic regulatory T (T(reg)) cells. ABA's beneficial effects on disease activity were completely abrogated in T cell-specific PPARγ null mice. Additionally, ABA improved colon histopathology, reduced blood F4/80(+)CD11b(+) monocytes, increased the percentage of CD4(+) T cells expressing the inhibitory molecule cytotoxic T lymphocyte antigen 4 in blood and enhanced the number of T(reg) cells in the mesenteric lymph nodes and colons of PPARγ-expressing but not T cell-specific PPARγ null mice. We conclude that dietary ABA ameliorates experimental inflammatory bowel disease by enhancing T(reg) cell accumulation in the colonic lamina propria through a PPARγ-dependent mechanism. |
| Databáze: | OpenAIRE |
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