title: Attenuation of dextran sodium sulphate induced colitis in matrix metalloproteinase-9 deficient mice.
abstract: OBJECTIVE
  To study whether matrix metalloproteinase-9 (MMP-9) is a key factor in epithelial damage in the dextran sodium sulphate (DSS) model of colitis in mice.
  
  
  METHODS
  MMP-9-deficient and wild-type (wt) mice were given 5% DSS in drinking water for 5 d followed by recovery up to 7 d. On d 5 and 12 after induction of colitis, gelatinases, MMP-2 and MMP-9, were measured in homogenates of colonic tissue by zymography and Western blot, whereas tissue inhibitor of metalloproteinases (TIMPs) were measured by reverse zymography. The gelatinolytic activity was also determined in supernatants of polymorphonuclear leukocytes (PMN) isolated from mice blood. Moreover, intestinal epithelial cells were stimulated with TNF-alpha to study whether these cells were able to produce MMPs. Finally, colonic mucosal lesions were measured by microscopic examination.
  
  
  RESULTS
  On d 5 of colitis, the activity of MMP-9 was increased in homogenates of colonic tissues (0.24+/-0.1 vs 21.3+/-6.4, P<0.05) and PMN from peripheral blood in wt (0.5+/-0.1 vs 10.4+/-0.7, P<0.05), but not in MMP-9-deficient animals. The MMP-9 activity was also up-regulated by TNF-alpha in epithelial intestinal cells (2.5+/-0.5 vs 14.7+/-3.0, P<0.05). Although colitis also led to increase of TIMP-1 activity, the MMP-9/TIMP-1 balance remained elevated. Finally, in the MMP-9-deficient colitic mice both the extent and severity of intestinal epithelial injury were significantly attenuated when compared with wt mice.
  
  
  CONCLUSIONS
  We conclude that DSS induced colitis is markedly attenuated in animals lacking MMP-9. This suggests that intestinal injury induced by DSS is modulated by MMP-9 and that inhibition of this gelatinase may reduce inflammation.
authors.affiliation: Gastroenterology Department and Research Unit, Hospital Universitario de Canarias, Tenerife, Spain.
authors.forename: Alfredo
authors.initials: A
authors.lastname: Santana
authors.forename: Carlos
authors.initials: C
authors.lastname: Medina
authors.forename: Maria-Cristina
authors.initials: MC
authors.lastname: Paz-Cabrera
authors.forename: Federico
authors.initials: F
authors.lastname: Díaz-Gonzalez
authors.forename: Esther
authors.initials: E
authors.lastname: Farré
authors.forename: Antonio
authors.initials: A
authors.lastname: Salas
authors.forename: Marek-W
authors.initials: MW
authors.lastname: Radomski
authors.forename: Enrique
authors.initials: E
authors.lastname: Quintero
mesh_terms: D000818:Animals; D002460:Cell Line; D003092:Colitis / Q000139:chemically induced / Q000201:enzymology* / Q000503:physiopathology*; D016264:Dextran Sulfate; D004195:Disease Models, Animal; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D020868:Gene Silencing; D006801:Humans; D007413:Intestinal Mucosa / Q000201:enzymology* / Q000473:pathology; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000235:genetics / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000235:genetics / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology
chemical_list: D019715:Tissue Inhibitor of Metalloproteinase-1; D014409:Tumor Necrosis Factor-alpha; D016264:Dextran Sulfate; D020780:Matrix Metalloproteinase 9