Journal of Leukocyte Biology Myeloid cells, immune suppression, tumor immunology
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Published online before print February 14, 2006
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© by The Society for Leukocyte Biology
Journal of Leukocyte Biology, doi:10.1189/jlb.1005544

Received for publication October 2, 2005.
Revised November 27, 2005.
Accepted for publication December 14, 2005.

Article

Matrix metalloproteinase-9 modulates intestinal injury in rats with transmural colitis

Carlos Medina *, Alfredo Santana *, Maria Cristina Paz *, Federico Díaz {dagger}, Esther Farre {ddagger}, Antonio Salas {ddagger}, Marek W. Radomski {sect}, and Enriquie Quintero *@

Servicios de *Gastroenterología y {dagger}Reumatología, Hospital Universitario de Canarias, La Laguna, Tenerife, Spain; {ddagger}Servicio de Anatomía Patológica, Hospital Mutua de Tarrasa, Barcelona, Spain; and {sect}Institute of Molecular Medicine for the Prevention of Human Diseases, University of Texas-Houston

@ To whom correspondence should be addressed. E-mail: equinter{at}ull.es.


  Abstract

Proteolysis and degradation of extracellular matrix by metalloproteinases (MMPs) may contribute to intestinal injury in inflammatory bowel disease. In the present study, we investigated the pathogenic role of gelatinases (MMP-9 and MMP-2) on transmural colonic injury in a rat model of chronic colitis, which was induced by intracolonic instillation of trinitrobenzene sulfonic acid (TNBS). The activity and expression of MMP-2 and MMP-9 were measured in colonic tissue and peripheral neutrophils by fluorescence, zymography, Western blot, or immunohistochemistry at different time-points. Furthermore, myeloperoxidase content in colonic homogenates was analyzed to evaluate inflammation. Finally, morphological changes were assessed following early or delayed administration of CGS-27023-A, a synthetic inhibitor of MMPs. We found that the induction of colitis led to a significant up-regulation in tissue gelatinase concentration, whereas no changes in collagenase activity were observed. In addition, up-regulation of pro-MMP-9, but not of pro-MMP-2, was found on Days 7 and 10 following the induction of colitis. Furthermore, transmural MMP-9 was detected by immunofluorescent staining in the inflamed tissue. Consistent with tissue samples, neutrophils from colitic rats showed a significantly increased activity of pro-MMP-9. Finally, early but not delayed treatment with CGS-27023-A attenuated colonic mucosal injury in rats with TNBS-induced colitis. In conclusion, up-regulation of MMP-9 in peripheral and colonic neutrophils modulates transmural colonic injury in rats with TNBS-induced colitis.

Key Words: inflammatory bowel disease • experimental colitis • trinitrobenzensulfonic acid • myeloperoxidase




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C. Medina and M. W. Radomski
Role of Matrix Metalloproteinases in Intestinal Inflammation
J. Pharmacol. Exp. Ther., September 1, 2006; 318(3): 933 - 938.
[Abstract] [Full Text] [PDF]


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