Dietary arachidonic acid-mediated effects on colon inflammation using transcriptome analysis.
Increased levels of n-6 arachidonic acid (AA), a precursor of pro-inflammatory eicosanoids, have been found in the colon mucosa of inflammatory bowel disease patients when compared with healthy subjects. The hypothesis was that dietary AA would aggravate colon inflammation by changing expression of genes in inflammatory signaling pathways. AA-enriched diet was fed to IL10 gene-deficient (Il10-/-) mice, model of a inflammatory bowel disease, and compared with Il10-/- mice fed an oleic acid control diet. Effects of AA on gene expression profiles during colitis were examined using whole genome microarray analysis. Dietary AA decreased the expression levels of some colonic genes in ER stress, complement system, nuclear respiratory factor 2-mediated oxidative stress and positive acute phase response pathways compared with Il10-/- mice fed an oleic acid diet. AA increased the expression levels of fatty acid catabolism genes, but decreased that of lipid synthesis genes during colitis, likely by sterol regulatory element binding transcription factor 1 and target gene regulation. A link has been suggested between AA and reduction of intestinal fibrosis by down-regulating the expression levels of pro-inflammatory and fibrotic marker genes. Contrary to the hypothesis, these findings suggest that dietary AA, in the present experimental conditions, is not pro-inflammatory, reduces ER stress and protects colonocytes from oxidative stress in Il10-/- mice.
Knoch
Bianca
B
Food, Metabolism and Microbiology Section, Food and Textiles Group, AgResearch Limited, Palmerston North, New Zealand.
Barnett
Matthew P G
MP
McNabb
Warren C
WC
Zhu
Shuotun
S
Park
Zaneta A
ZA
Khan
Anar
A
Roy
Nicole C
NC
D000818:Animals; D016718:Arachidonic Acid / Q000008:administration & dosage / Q000494:pharmacology*; D003106:Colon / Q000503:physiopathology*; D004032:Diet; D004195:Disease Models, Animal; D017353:Gene Deletion; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D005838:Genotype; D006801:Humans; D007249:Inflammation / Q000235:genetics* / Q000503:physiopathology*; D015212:Inflammatory Bowel Diseases / Q000139:chemically induced / Q000503:physiopathology; D016753:Interleukin-10 / Q000172:deficiency* / Q000235:genetics; D007413:Intestinal Mucosa / Q000473:pathology / Q000503:physiopathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D020411:Oligonucleotide Array Sequence Analysis; D012016:Reference Values; D020133:Reverse Transcriptase Polymerase Chain Reaction; D051780:Sterol Regulatory Element Binding Protein 1 / Q000235:genetics
C497388:Srebf1 protein, mouse; D051780:Sterol Regulatory Element Binding Protein 1; D016753:Interleukin-10; D016718:Arachidonic Acid