MUSCLE HYPER-CONTRACTILITY IN A MURINE MODEL OFPOST-INFECTIVE IRRITABLE BOWEL SYNDROME - ROLE OF TGFb1 AND COX-2

H Akiho, Y Deng, P Blennerhassett, H Kanbayashi, WI Khan, SM Collins

Intestinal Disease Research Program, McMaster University, Hamilton, Ontario

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 hyper-contractility. This study examined whether muscle hyper-contractility at the post-infective (PI) state is maintained at the level of smooth muscle cells, and examined putative mediators.

METHODS: Muscle contraction and mRNA or protein expression of cytokines were examined from longitudinal muscle cells of NIH Swiss mice infected with or without Trichinella spiralis or incubated with or without cytokines.

RESULTS: In acute phase of infection, Th2 cytokines, IL-4 or IL-13, TGFb1 and COX-2 were increased in the muscle. In PI phase of infection, Th2 cytokines returned to normal, but TGFb1 and COX-2 remained in the muscle. Exposure of muscle cells to IL-4 or IL-13 increased TGFb1 and PGE₂ protein. Exposure of muscle cells to IL-4, IL-13 or TGFb1 increased PGE₂ and COX-2 protein. Incubation of IL-4, IL-13 or TGFb1 to the LMMP enhanced carbachol or PGE₂-induced muscle contractility. COX-2 inhibitor attenuated TGFb1-induced muscle hyper-contractility.

CONCLUSIONS: Our results indicate that post-infective hyper-contractility of enteric muscle is a property of the muscle cell rather than a syncytium. We propose that it is initiated by Th2 cytokines, IL-4 and IL-13, and maintained by TGFb1 acting via COX-2 at the level of the muscle cells.

NEXT ABSTRACT