Mechanisms underlying the maintenance of muscle hypercontractility in a model of postinfective gut dysfunction.
Gastroenterology
; 129(1): 131-41, 2005 Jul.
Article
em En
| MEDLINE
| ID: mdl-16012943
ABSTRACT
BACKGROUND & AIMS:
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.
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Base de dados:
MEDLINE
Assunto principal:
Triquinelose
/
Trichinella spiralis
/
Síndrome do Intestino Irritável
/
Gastroenterite
/
Motilidade Gastrointestinal
Tipo de estudo:
Prognostic_studies
/
Risk_factors_studies
Limite:
Animals
Idioma:
En
Ano de publicação:
2005
Tipo de documento:
Article