BACKGROUND AND AIM: Matrix metalloproteinases (MMPs) have been implicated in tissue remodelling and ulceration in inflammatory bowel disease and coeliac disease. Studies to date have concluded that stromelysin 1 is functionally involved in mucosal degradation. However, there are many other MMPs whose function in the gut is currently unknown. This work had two aims: firstly, to use gene array technology to measure changes in MMP and tissue inhibitor of metalloproteinase (TIMP) expression in a model of T cell mediated injury in the gut, and secondly, to correlate data from gene arrays with that generated by in situ hybridisation. METHODS: T cells in explants of human fetal gut were activated with pokeweed mitogen or anti-CD3 plus interleukin 12. Gene array analysis and in situ hybridisation were performed to investigate changes in MMP gene expression. RESULTS: Both gene array analysis and in situ hybridisation indicated marked upregulation of stromelysin 2 and macrophage metalloelastase expression in the explants associated with mucosal destruction. The arrays also confirmed our previous observation that interstitial collagenase (MMP-1), stromelysin 1 (MMP-3), and gelatinase B (MMP-9) are upregulated but there was no change in MMP-2, -7, -8, -9, -11, -13, -14-17, or -19. Following T cell activation, transcripts for TIMPs were reduced. CONCLUSIONS: These results show that there is differential upregulation of MMPs during T cell responses in the gut and suggest that further studies on the role of stromelysin 2 and macrophage metalloelastase may show that they have a functional role. In addition, the increase in MMPs and reduction in TIMPs suggest that the protease/antiprotease balance in the mucosa may determine the extent of mucosal degradation.
BACKGROUND AND AIM: Matrix metalloproteinases (MMPs) have been implicated in tissue remodelling and ulceration in inflammatory bowel disease and coeliac disease. Studies to date have concluded that stromelysin 1 is functionally involved in mucosal degradation. However, there are many other MMPs whose function in the gut is currently unknown. This work had two aims: firstly, to use gene array technology to measure changes in MMP and tissue inhibitor of metalloproteinase (TIMP) expression in a model of T cell mediated injury in the gut, and secondly, to correlate data from gene arrays with that generated by in situ hybridisation. METHODS: T cells in explants of human fetal gut were activated with pokeweed mitogen or anti-CD3 plus interleukin 12. Gene array analysis and in situ hybridisation were performed to investigate changes in MMP gene expression. RESULTS: Both gene array analysis and in situ hybridisation indicated marked upregulation of stromelysin 2 and macrophage metalloelastase expression in the explants associated with mucosal destruction. The arrays also confirmed our previous observation that interstitial collagenase (MMP-1), stromelysin 1 (MMP-3), and gelatinase B (MMP-9) are upregulated but there was no change in MMP-2, -7, -8, -9, -11, -13, -14-17, or -19. Following T cell activation, transcripts for TIMPs were reduced. CONCLUSIONS: These results show that there is differential upregulation of MMPs during T cell responses in the gut and suggest that further studies on the role of stromelysin 2 and macrophage metalloelastase may show that they have a functional role. In addition, the increase in MMPs and reduction in TIMPs suggest that the protease/antiprotease balance in the mucosa may determine the extent of mucosal degradation.
Authors: A B de Coignac; G Elson; Y Delneste; G Magistrelli; P Jeannin; J P Aubry; O Berthier; D Schmitt; J Y Bonnefoy; J F Gauchat Journal: Eur J Biochem Date: 2000-06
Authors: S L Pender; M T Salmela; G Monteleone; D Schnapp; C McKenzie; J Spencer; S Fong; U Saarialho-Kere; T T MacDonald Journal: Am J Pathol Date: 2000-12 Impact factor: 4.307
Authors: Pallavi Garg; Sabrina Jeppsson; Guillaume Dalmasso; Amr M Ghaleb; Beth B McConnell; Vincent W Yang; Andrew T Gewirtz; Didier Merlin; Shanthi V Sitaraman Journal: Gastroenterology Date: 2011-06-30 Impact factor: 22.682
Authors: G Monteleone; R Caruso; D Fina; I Peluso; V Gioia; C Stolfi; M C Fantini; F Caprioli; R Tersigni; L Alessandroni; T T MacDonald; F Pallone Journal: Gut Date: 2006-05-08 Impact factor: 23.059
Authors: B Diosdado; M C Wapenaar; L Franke; K J Duran; M J Goerres; M Hadithi; J B A Crusius; J W R Meijer; D J Duggan; C J J Mulder; F C P Holstege; C Wijmenga Journal: Gut Date: 2004-07 Impact factor: 23.059