Suppression of intestinal inflammation and inflammation-driven colon cancer in mice by dietary sphingomyelin: importance of peroxisome proliferator-activated receptor γ expression

被引:64
作者
Mazzei, Joseph C. [1 ]
Zhou, Hui [1 ]
Brayfield, Bradley P. [1 ]
Hontecillas, Raquel [2 ]
Bassaganya-Riera, Josep [2 ]
Schmelz, Eva M. [1 ]
机构
[1] Virginia Polytech Inst & State Univ, Virginia Bioinformat Inst, Dept Human Nutr Foods & Exercise, Blacksburg, VA 24061 USA
[2] Virginia Polytech Inst & State Univ, Virginia Bioinformat Inst, Lab Nutr Immunol & Mol Med, Blacksburg, VA 24061 USA
关键词
Sphingomyelin; Inflammation; Macrophages; CD4+T cells; Colon cancer; PPAR-GAMMA; CRYPT FOCI; CELL-PROLIFERATION; COLORECTAL-CANCER; GENE-EXPRESSION; INDUCED COLITIS; CF1; MICE; ACID; SPHINGOLIPIDS; GROWTH;
D O I
10.1016/j.jnutbio.2010.09.017
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Inflammation of the gastrointestinal tract increases the risk of developing colon cancer especially in younger adults. Dietary compounds are not only associated with the etiology of inflammation and colon cancer but also in their prevention. Sphingolipid metabolites have been shown to play a role in the initiation and perpetuation of inflammatory responses. In the present study, we investigated the suppression of dextran sodium sulfate-induced colitis and azoxymethane-induced colon cancer by dietary sphingomyelin (SM) in mice that lack functional peroxisome proliferator-activated receptor gamma (PPAR-gamma) in intestinal epithelial and immune cells. Dietary SM decreased disease activity and colonic inflammatory lesions in mice of both genotypes but more efficiently in mice expressing PPAR-gamma. The increased survival and suppression of tumor formation in the SM-fed mice appeared to be independent of PPAR-gamma expression in immune and epithelial cells. Using a real-time polymerase chain reaction array, we detected an up-regulation in genes involved in Th1 (interferon gamma) and Th17 (interleukin [IL]-17 and IL-23) responses despite the reduced inflammation scores. However, the genes involved in Th2 (IL-4, IL-13 and IL-13ra2) and Treg (IL-10rb) anti-inflammatory responses were up-regulated in a PPAR-gamma-dependent manner. In line with the PPAR-gamma dependency of our in vivo findings, treatment of RAW macrophages with sphingosine increased the PPAR-gamma reporter activity. In conclusion, dietary SM modulated inflammatory responses at the early stages of the disease by activating PPAR-gamma, but its anticarcinogenic effects followed a PPAR-gamma-independent pattern. (C) 2011 Elsevier Inc. All rights reserved.
引用
收藏
页码:1160 / 1171
页数:12
相关论文
共 64 条
[1]   Conditional disruption of the peroxisome proliferator-activated receptor γ gene in mice results in lowered expression of ABCA1, ABCG1, and apoE in macrophages and reduced cholesterol efflux [J].
Akiyama, TE ;
Sakai, S ;
Lambert, G ;
Nicol, CJ ;
Matsusue, K ;
Pimprale, S ;
Lee, YH ;
Ricote, M ;
Glass, CK ;
Brewer, HB ;
Gonzalez, FJ .
MOLECULAR AND CELLULAR BIOLOGY, 2002, 22 (08) :2607-2619
[2]  
[Anonymous], NUTR PHYS ACT PREV C
[3]  
[Anonymous], 2009, SEER Cancer Statistics Review, 1975-2006
[4]   PPARγ is required for placental, cardiac, and adipose tissue development [J].
Barak, Y ;
Nelson, MC ;
Ong, ES ;
Jones, YZ ;
Ruiz-Lozano, P ;
Chien, KR ;
Koder, A ;
Evans, RM .
MOLECULAR CELL, 1999, 4 (04) :585-595
[5]   Bioactive sphingolipids: metabolism and function [J].
Bartke, Nana ;
Hannun, Yusuf A. .
JOURNAL OF LIPID RESEARCH, 2009, 50 :S91-S96
[6]   Activation of PPAR γ and δ by conjugated linoleic acid mediates protection from experimental inflammatory bowel disease [J].
Bassaganya-Riera, J ;
Reynolds, K ;
Martino-Catt, S ;
Cui, YZ ;
Hennighausen, L ;
Gonzalez, F ;
Rohrer, J ;
Benninghoff, AU ;
Hontecillas, R .
GASTROENTEROLOGY, 2004, 127 (03) :777-791
[7]   Peroxisome Proliferator-Activated Receptors: The Nutritionally Controlled Molecular Networks that Integrate Inflammation, Immunity and Metabolism [J].
Bassaganya-Riera, Josep ;
Guri, Amir ;
King, Jennifer ;
Hontecillas, Raquel .
CURRENT NUTRITION & FOOD SCIENCE, 2005, 1 (02) :179-187
[8]   PPAR γ is highly expressed in F4/80hi adipose tissue macrophages and dampens adipose-tissue inflammation [J].
Bassaganya-Riera, Josep ;
Misyak, Sarah ;
Guri, Amir J. ;
Hontecillas, Raquel .
CELLULAR IMMUNOLOGY, 2009, 258 (02) :138-146
[9]  
Bauer J, 2009, PLOS ONE, Ve7197, P4
[10]  
BIERI JG, 1977, J NUTR, V107, P1394