Abscisic acid ameliorates experimental IBD by downregulating cellular adhesion molecule expression and suppressing immune cell infiltration.
OBJECTIVE
Abscisic acid (ABA) has shown effectiveness in ameliorating inflammation in obesity, diabetes and cardiovascular disease models. The objective of this study was to determine whether ABA prevents or ameliorates experimental inflammatory bowel disease (IBD).


METHODS
C57BL/6J mice were fed diets with or without ABA (100mg/kg) for 35 days prior to challenge with 2.5% dextran sodium sulfate (DSS). The severity of clinical disease was assessed daily. Colonic mucosal lesions were evaluated by histopathology, and cellular adhesion molecular and inflammatory markers were assayed by real-time quantitative PCR. Flow cytometry was used to quantify leukocyte populations in the blood, spleen, and mesenteric lymph nodes (MLN). The effect of ABA on cytotoxic T-lymphocyte antigen 4 (CTLA-4) expression in splenocytes was also investigated.


RESULTS
ABA significantly ameliorated disease activity, colitis and reduced colonic leukocyte infiltration and inflammation. These improvements were associated with downregulation in vascular cell adhesion marker-1 (VCAM-1), E-selectin, and mucosal addressin adhesion marker-1 (MAdCAM-1) expression. ABA also increased CD4(+) and CD8(+) T-lymphocytes in blood and MLN and regulatory T cells in blood. In vitro, ABA increased CTLA-4 expression through a PPAR γ-dependent mechanism.


CONCLUSIONS
We conclude that ABA ameliorates gut inflammation by modulating T cell distribution and adhesion molecule expression.
Laboratory of Nutritional Immunology & Molecular Nutrition, Virginia Bioinformatics Institute, Virginia Polytechnic Institute and State University, Blacksburg, VA 24061, USA.
Amir J
AJ
Guri
Raquel
R
Hontecillas
Josep
J
Bassaganya-Riera
D000040:Abscisic Acid / Q000494:pharmacology*; D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D060908:CTLA-4 Antigen; D002448:Cell Adhesion; D015815:Cell Adhesion Molecules / Q000378:metabolism; D004195:Disease Models, Animal; D015536:Down-Regulation; D019040:E-Selectin / Q000378:metabolism; D015212:Inflammatory Bowel Diseases / Q000276:immunology / Q000517:prevention & control*; D007413:Intestinal Mucosa / Q000276:immunology / Q000378:metabolism; D007962:Leukocytes / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D009088:Mucoproteins; D009765:Obesity / Q000473:pathology; D047495:PPAR gamma / Q000378:metabolism; D019010:Vascular Cell Adhesion Molecule-1 / Q000378:metabolism
D015703:Antigens, CD; D060908:CTLA-4 Antigen; D015815:Cell Adhesion Molecules; C556707:Ctla4 protein, mouse; D019040:E-Selectin; C489082:Madcam1 protein, mouse; D009088:Mucoproteins; D047495:PPAR gamma; D019010:Vascular Cell Adhesion Molecule-1; D000040:Abscisic Acid