title: Mechanisms underlying the maintenance of muscle hypercontractility in a model of postinfective gut dysfunction.
abstract: OBJECTIVE
  Acute gastroenteritis is a strong risk factor for the development of irritable bowel syndrome (IBS). We have developed an animal model in which transient acute infection leads to persistent muscle hypercontractility. Here, we investigate the mechanisms underlying the maintenance of this hypercontractility in the postinfective (PI) state.
  
  
  METHODS
  Muscle contraction and messenger RNA (mRNA) or protein expression of cytokines were examined from jejunal longitudinal muscle cells of NIH Swiss mice infected with Trichinella spiralis or incubated with or without cytokines.
  
  
  RESULTS
  During acute infection, interleukin (IL)-4 or IL-13, transforming growth factor (TGF)-beta1, and cyclooxygenase (COX)-2 were increased in the muscle layer ( P < .05). In the PI phase of the model, T helper (Th)2 cytokines returned to normal, but TGF-beta1 remained in the muscle ( P < .05). Exposure of muscle cells to IL-4 or IL-13 increased TGF-beta1 ( P < .01), COX-2 protein, and prostaglandin (PG)E 2 . Exposure of muscle cells to TGF-beta1 increased PGE 2 ( P < .05) and COX-2 protein. Incubation of tissue with IL-4, IL-13, TGF-beta1, or PGE 2 enhanced carbachol-induced muscle cell contractility ( P < .05). COX-2 inhibitor attenuated TGF-beta1-induced muscle hypercontractility ( P < .05).
  
  
  CONCLUSIONS
  These results support the hypothesis that Th2 cytokines induce muscle hypercontractility during infection by a direct action on smooth muscle. The maintenance of hypercontractility results from Th2 cytokine-induced expression of TGF-beta1 and the subsequent up-regulation of COX-2 and PGE 2 at the level of the smooth muscle cell. We propose that PI gut dysfunction reflects mediator production in the neuromuscular tissues and that this may occur in PI-IBS.
authors: Intestinal Diseases Research Program, Department of Medicine, McMaster University, Hamilton, Ontario, Canada.
authors: Hirotada
authors: H
authors: Akiho
authors: Yikang
authors: Y
authors: Deng
authors: Patricia
authors: P
authors: Blennerhassett
authors: Hiroshi
authors: H
authors: Kanbayashi
authors: Stephen M
authors: SM
authors: Collins
mesh_terms: D000208:Acute Disease; D000818:Animals; D002217:Carbachol / Q000494:pharmacology; D002478:Cells, Cultured; D018679:Cholinergic Agonists / Q000494:pharmacology; D002908:Chronic Disease; D051546:Cyclooxygenase 2; D015232:Dinoprostone / Q000378:metabolism; D004195:Disease Models, Animal; D005759:Gastroenteritis / Q000469:parasitology / Q000503:physiopathology*; D005769:Gastrointestinal Motility; D018793:Interleukin-13 / Q000494:pharmacology; D015847:Interleukin-4 / Q000494:pharmacology; D043183:Irritable Bowel Syndrome / Q000469:parasitology / Q000503:physiopathology*; D008297:Male; D051379:Mice; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000166:cytology / Q000378:metabolism / Q000503:physiopathology; D016133:Polymerase Chain Reaction; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism; D011509:Proteoglycans / Q000235:genetics; D012333:RNA, Messenger / Q000032:analysis; D019948:Receptors, Interleukin-4 / Q000235:genetics; D018125:Receptors, Transforming Growth Factor beta / Q000235:genetics; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000378:metabolism; D053773:Transforming Growth Factor beta1; D017160:Trichinella spiralis; D014235:Trichinellosis / Q000150:complications* / Q000503:physiopathology
chemical_list: D018679:Cholinergic Agonists; D018793:Interleukin-13; D011509:Proteoglycans; D012333:RNA, Messenger; D019948:Receptors, Interleukin-4; D018125:Receptors, Transforming Growth Factor beta; C508961:Tgfb1 protein, mouse; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; C071736:betaglycan; D015847:Interleukin-4; D002217:Carbachol; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases; D015232:Dinoprostone