Upregulation of matrix metalloproteinases in a model of T cell mediated tissue injury in the gut: analysis by gene array and in situ hybridisation. Issue 4 (1st October 2002)

• Record Type: Journal Article
• Authors: Salmela, M T; MacDonald, T T; Black, D; Irvine, B; Zhuma, T; Saarialho-Kere, U; Pender, S L F
• Is Part Of: Gut. Volume 51:Issue 4(2002)
• Page Start: 540
• Page End: 547
• Publication Date: 2002-10-01
• Subjects: collagenase -- matrilysin -- metalloelastase -- tissue inhibitor of metalloproteinase -- stromelysin; PWM, pokeweed mitogen -- IL-12, interleukin-12 -- IBD, inflammatory bowel disease -- ECM, extracellular matrix -- LP, lamina propria -- α-SMA, α smooth muscle actin -- MMP, matrix metalloproteinase -- TIMP, tissue inhibitor of metalloproteinase -- TNF-α, tumour necrosis factor α; Gastroenterology -- Periodicals; 616.33
• DOI: 10.1136/gut.51.4.540
• Languages: English
• ISSNs: 0017-5749

Abstract

Abstract : 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.