title: Prostaglandin E₂ and polyenylphosphatidylcholine protect against intestinal fibrosis and regulate myofibroblast function.
abstract: BACKGROUND
  Intestinal fibrosis is a serious and often recurrent complication of inflammatory bowel disease despite surgical intervention. The anti-fibrotic potential of prostaglandin E2 (PGE2) and polyenylphosphatidylcholine (PC) was investigated using the murine model of 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced chronic intestinal inflammation and fibrosis, and murine and human intestinal myofibroblasts.
  
  
  METHODS
  Mice were treated with TNBS enemas weekly for 2 or 6 weeks ± PGE2 (10 mg/kg/day orally) or PC (200 mg/kg/day orally). Inflammation and fibrosis were histologically assessed and scored. Pro-inflammatory cytokines, TLR4, and ECM-related gene expression from the colonic tissue and cultured myofibroblasts were assessed by RT-qPCR. The levels of α-SMA(+) staining and endogenous PGE2 in vivo were also assessed.
  
  
  RESULTS
  Both PGE2 and PC treatment significantly decreased TNBS-induced intestinal inflammation and excess collagen deposition in vivo. This was accompanied by decreased α-SMA(+) staining in the lamina propria and lower collagen type I (COL1α1) expression. Endogenous PGE2 levels demonstrated that PC was not being converted into PGE2, thus mediating its effects primarily via PGE2-independent pathways. Both PGE2 and the PC isoform, 1,2-dilinoleoylphosphatidylcholine (DLPC), regulated primary mouse myofibroblast and CCD-18co COL1α1 production, and induced lower collagen type I to III and TGF-β1 to TGF-β3 ratios, demonstrating their ability to induced normal healing in the presence of phorbol 12-myristate 13-acetate (protein kinase C-dependent inducer of collagen production).
  
  
  CONCLUSIONS
  PGE2 and PC both have potent anti-fibrogenic potentials in their ability to regulate inflammatory cell and myofibroblast accumulation within inflamed tissue, to decrease pro-inflammatory cytokine expression and to maintain normal healing in an inflammatory environment.
authors: Fremantle Unit, School of Medicine and Pharmacology, Level 6, T Block, Fremantle Hospital, University of Western Australia, Alma Street, Fremantle, WA, 6010, Australia, angela.chew@uwa.edu.au.
authors: Angela C
authors: AC
authors: Baird
authors: Frances
authors: F
authors: Lloyd
authors: Ian C
authors: IC
authors: Lawrance
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000032:analysis; D016207:Cytokines / Q000032:analysis; D015232:Dinoprostone / Q000494:pharmacology*; D004195:Disease Models, Animal; D005260:Female; D005355:Fibrosis / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D015870:Gene Expression; D006801:Humans; D007124:Immunoenzyme Techniques; D015212:Inflammatory Bowel Diseases / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D058628:Myofibroblasts / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology*; D010713:Phosphatidylcholines / Q000494:pharmacology*; D060888:Real-Time Polymerase Chain Reaction; D014302:Trinitrobenzenesulfonic Acid
chemical_list: D015415:Biomarkers; D016207:Cytokines; D010713:Phosphatidylcholines; C005152:lipostabil; D014302:Trinitrobenzenesulfonic Acid; D015232:Dinoprostone
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