title: Diet-Induced Hyperhomocysteinaemia Increases Intestinal Inflammation in an Animal Model of Colitis.
abstract: BACKGROUND
  Hyperhomocysteinaemia [HHcy] is a common phenomenon observed in patients with inflammatory bowel disease [IBD]. Homocysteine is a pro-inflammatory molecule and has been identified as a risk factor for cardiovascular and cerebral diseases. Whether HHcy contributes to the chronic inflammation of the colon in IBD has rarely been explored. The aim of this study was to investigate the effect of HHcy on dextran sulphate sodium [DSS]-induced colitis.
  
  
  METHODS
  Wistar rats were randomly divided into eight groups: [1] Control; [2] HHcy; [3] p38 inhibitor; [4] DSS; [5] HHcy + DSS; [6] HHcy + DSS+p38 inhibitor; [7] HHcy + DSS [21 days]; and [8] HHcy + DSS + folate [21 days]. Colitis was induced by 5% DSS. HHcy was induced by the normal rodent diet containing 1.7% methionine. The mRNA expression of interleukin 17 [IL-17] was detected by qRT-PCR. The protein expressions of IL-17, retinoid-related orphan nuclear receptor-γt [RORγt], p38 MAPK, phosphorylated-p38 MAPK, cytosolic phospolipaseA2 [cPLA2], phosphorylated-cPLA2, and cyclooxygenase 2 [COX2] were detected by immunoblot analysis.
  
  
  RESULTS
  The rats of the HHcy + DSS group had significantly higher myeloperoxidase [MPO] activity, DAI score, and histological score. HHcy significantly increased the plasma concentration, the colonic mRNA, and the protein levels of IL-17. HHcy also activated p38 MAPK and cPLA2, and increased the protein levels of COX2 and RORγt as well as the plasma level of prostaglandin E2 [PGE2]. Folate supplementation down-regulated homocysteine-induced IL-17 and RORγt expressions.
  
  
  CONCLUSIONS
  HHcy aggravated DSS-induced colitis by stimulating IL-17 expression via the p38/cPLA2/COX2/PGE2 signalling pathway. The folate supplementation may represent a novel approach to treating the chronic intestinal inflammation of IBD exacerbated by HHcy.
authors.affiliation: Department of Gastroenterology, Zhongnan Hospital of Wuhan University, Wuhan, P.R. China Hubei Clinical Center & Key Laboratory of Intestinal & Colorectal Diseases, Wuhan, P.R. China.
authors.forename: Siying
authors.initials: S
authors.lastname: Zhu
authors.affiliation: Department of Gastroenterology, Zhongnan Hospital of Wuhan University, Wuhan, P.R. China Hubei Clinical Center & Key Laboratory of Intestinal & Colorectal Diseases, Wuhan, P.R. China.
authors.forename: Jin
authors.initials: J
authors.lastname: Li
authors.affiliation: Hubei Clinical Center & Key Laboratory of Intestinal & Colorectal Diseases, Wuhan, P.R. China.
authors.forename: Yuntao
authors.initials: Y
authors.lastname: Bing
authors.affiliation: Hubei Clinical Center & Key Laboratory of Intestinal & Colorectal Diseases, Wuhan, P.R. China.
authors.forename: Wenfeng
authors.initials: W
authors.lastname: Yan
authors.affiliation: Department of Gastroenterology, Zhongnan Hospital of Wuhan University, Wuhan, P.R. China Hubei Clinical Center & Key Laboratory of Intestinal & Colorectal Diseases, Wuhan, P.R. China.
authors.forename: Youqing
authors.initials: Y
authors.lastname: Zhu
authors.affiliation: Department of Gastroenterology, Zhongnan Hospital of Wuhan University, Wuhan, P.R. China Hubei Clinical Center & Key Laboratory of Intestinal & Colorectal Diseases, Wuhan, P.R. China.
authors.forename: Bing
authors.initials: B
authors.lastname: Xia
authors.affiliation: Department of Gastroenterology, Zhongnan Hospital of Wuhan University, Wuhan, P.R. China Hubei Clinical Center & Key Laboratory of Intestinal & Colorectal Diseases, Wuhan, P.R. China chenmin8106@aliyun.com.
authors.forename: Min
authors.initials: M
authors.lastname: Chen
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D003092:Colitis / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology*; D003106:Colon / Q000378:metabolism / Q000473:pathology*; D016264:Dextran Sulfate; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D020138:Hyperhomocysteinemia / Q000150:complications* / Q000209:etiology; D015151:Immunoblotting; D008297:Male; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012720:Severity of Illness Index
chemical_list: D015415:Biomarkers; D016264:Dextran Sulfate
keywords: Homocysteine; inflammatory bowel disease; interleukin 17