Activation of PPARγ and δ by dietary punicic acid ameliorates intestinal inflammation in mice

被引:60
作者
Bassaganya-Riera, Josep [1 ]
DiGuardo, Margaret [2 ]
Climent, Montse [1 ]
Vives, Cristina [1 ]
Carbo, Adria [1 ]
Jouni, Zeina E. [3 ]
Einerhand, Alexandra W. C. [4 ]
O'Shea, Marianne [4 ]
Hontecillas, Raquel [1 ]
机构
[1] Virginia Polytech Inst & State Univ, Virginia Bioinformat Inst, Lab Nutr Immunol & Mol Nutr, Blacksburg, VA 24061 USA
[2] Nutr Therapeut Inc, Blacksburg, VA 24061 USA
[3] Mead Johnson Nutr, Evansville, IN 47721 USA
[4] Lipid Nutr BV, Channahon, IL 60410 USA
关键词
Inflammatory bowel disease; PPAR; Punicic acid; RECEPTOR-GAMMA; GENE-EXPRESSION; COLON INFLAMMATION; BOWEL-DISEASE; PIG MODEL; T-CELLS; COLITIS; ALPHA; PROTECTION; FAT;
D O I
10.1017/S0007114511001188
中图分类号
R15 [营养卫生、食品卫生]; TS201 [基础科学];
学科分类号
100403 [营养与食品卫生学];
摘要
The goal of the present study was to elucidate the mechanisms of immunoregulation by which dietary punicic acid (PUA) prevents or ameliorates experimental inflammatory bowel disease (IBD). The expression of PPAR gamma and delta, their responsive genes and pro-inflammatory cytokines was assayed in the colonic mucosa. Immune cell-specific PPAR gamma null, PPAR delta knockout and wild-type mice were treated with PUA and challenged with 2.5% dextran sodium sulphate (DSS). The prophylactic efficacy of PUA was examined in an IL-10(-/-) model of IBD. The effect of PUA on the regulatory T-cell (Treg) compartment was also examined in mice with experimental IBD. PUA ameliorated spontaneous pan-enteritis in IL-10(-/-) mice and DSS colitis, up-regulated Foxp3 expression in Treg and suppressed TNF-alpha, but the loss of functional PPAR gamma or delta impaired these anti-inflammatory effects. At the cellular level, the macrophage-specific deletion of PPAR gamma caused a complete abrogation of the protective effect of PUA, whereas the deletion of PPAR delta or intestinal epithelial cell-specific PPAR gamma decreased its anti-inflammatory efficacy. We provide in vivo molecular evidence demonstrating that PUA ameliorates experimental IBD by regulating macrophage and T-cell function through PPAR gamma- and delta-dependent mechanisms.
引用
收藏
页码:878 / 886
页数:9
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