Hontecillas Raquel, Bassaganya-Riera Josep
Nutritional Immunology and Molecular Medicine Laboratory, Center for Modeling Immunity to Enteric Pathogens, Virginia Bioinformatics Institute, Virginia Tech, Blacksburg, Virginia, 24060, United States of America.
ESPEN J. 2012 Oct 1;7(5):e189-e195. doi: 10.1016/j.clnme.2012.07.002.
BACKGROUND & AIMS: Dietary abscisic acid (ABA) has shown efficacy in ameliorating experimental IBD in mice through mechanisms requiring expression of peroxisome proliferator activated-receptor γ (PPAR γ) in immune cells. The goal of this study was to determine whether PPAR γ expression in colonic epithelial cells is required for the anti-inflammatory actions of ABA.
Conditional knockout mice expressing a transgenic recombinase in intestinal epithelial cells under the control of a villin promoter (PPAR γ flfl; Villin Cre+ or VC+) with defective expression of PPAR γ in intestinal cells (IEC) and PPAR γ-expressing wild type (PPAR γ flfl; Villin Cre- or VC-) mice in a C57BL/6 background were fed diets with and without ABA (0.1 g/kg) for 35 days and challenged with 2.5% dextran sodium sulfate (DSS) in the drinking water for 7 days. Clinical disease severity was assessed daily and colonic lesions on day 7 through macroscopic and histopathological examination. Immune cell phenotypes were examined systemically and at the mesenteric lymph nodes (MLN). Epithelial gene expression was assayed in the colon.
Dietary ABA-supplementation prevented colitis, reduced disease severity, improved colonic histopathology, and upregulated epithelial lanthionine synthetase C-like protein 2 (LANCL2) expression in VC+ mice. Dietary ABA significantly increased the percentages of MLN CD4+IL-10+ T cells, and blood CD4+CD25+FoxP3+ T cells and CD8+IL-10+ T cells.
Expression of PPAR γ in IECs was not required for the anti-inflammatory efficacy of ABA in IBD. LANCL2 in IECs and T cell-derived IL-10 may be implicated in the mechanism underlying ABA's immune modulatory activity in IBD.
膳食脱落酸（ABA）已显示出通过免疫细胞中过氧化物酶体增殖物激活受体γ（PPARγ）表达所需的机制来改善小鼠实验性炎症性肠病（IBD）的功效。本研究的目的是确定结肠上皮细胞中PPARγ的表达对于ABA的抗炎作用是否必要。
在C57BL/6背景下，在肠绒毛蛋白启动子控制下在肠上皮细胞中表达转基因重组酶的条件性敲除小鼠（PPARγflfl；Villin Cre+或VC+），其肠细胞（IEC）中PPARγ表达缺陷，以及表达PPARγ的野生型（PPARγflfl；Villin Cre-或VC-）小鼠，给予含或不含ABA（0.1 g/kg）的饮食35天，并在饮用水中给予2.5%葡聚糖硫酸钠（DSS）刺激7天。每天评估临床疾病严重程度，并在第7天通过宏观和组织病理学检查评估结肠病变。对全身和肠系膜淋巴结（MLN）的免疫细胞表型进行检查。测定结肠中的上皮基因表达。
补充膳食ABA可预防结肠炎，降低疾病严重程度，改善结肠组织病理学，并上调VC+小鼠中上皮羊毛硫氨酸合成酶C样蛋白2（LANCL2）的表达。膳食ABA显著增加了MLN CD4+IL-10+ T细胞、血液CD4+CD25+FoxP3+ T细胞和CD8+IL-10+ T细胞的百分比。
IEC中PPARγ的表达对于ABA在IBD中的抗炎功效并非必需。IEC中的LANCL2和T细胞衍生的IL-10可能参与了ABA在IBD中免疫调节活性的潜在机制。
