title: Activation of PPARγ and δ by dietary punicic acid ameliorates intestinal inflammation in mice.
abstract: 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 PPARγ and δ, their responsive genes and pro-inflammatory cytokines was assayed in the colonic mucosa. Immune cell-specific PPARγ null, PPARδ 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-α, but the loss of functional PPARγ or δ impaired these anti-inflammatory effects. At the cellular level, the macrophage-specific deletion of PPARγ caused a complete abrogation of the protective effect of PUA, whereas the deletion of PPARδ or intestinal epithelial cell-specific PPARγ 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 PPARγ- and δ-dependent mechanisms.
authors: Laboratory of Nutritional Immunology and Molecular Nutrition, Virginia Bioinformatics Institute, Virginia Polytechnic Institute and State University, Blacksburg, VA 24061, USA. jbassaga@vt.edu
authors: Josep
authors: J
authors: Bassaganya-Riera
authors: Margaret
authors: M
authors: DiGuardo
authors: Montse
authors: M
authors: Climent
authors: Cristina
authors: C
authors: Vives
authors: Adria
authors: A
authors: Carbo
authors: Zeina E
authors: ZE
authors: Jouni
authors: Alexandra W C
authors: AW
authors: Einerhand
authors: Marianne
authors: M
authors: O'Shea
authors: Raquel
authors: R
authors: Hontecillas
mesh_terms: D000821:Animal Feed; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D017353:Gene Deletion; D007249:Inflammation; D015212:Inflammatory Bowel Diseases / Q000188:drug therapy*; D016753:Interleukin-10 / Q000235:genetics; D007413:Intestinal Mucosa / Q000378:metabolism* / Q000382:microbiology*; D008042:Linolenic Acids / Q000494:pharmacology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D047494:PPAR delta / Q000378:metabolism*; D047495:PPAR gamma / Q000378:metabolism*; D013601:T-Lymphocytes / Q000166:cytology; D050378:T-Lymphocytes, Regulatory / Q000166:cytology
chemical_list: D000893:Anti-Inflammatory Agents; D008042:Linolenic Acids; D047494:PPAR delta; D047495:PPAR gamma; D016753:Interleukin-10; C519714:punicic acid