Induction of a fibrogenic response in mouse colon by overexpression of monocyte chemoattractant protein 1.
Gut
; 55(5): 662-70, 2006 May.
Article
en En
| MEDLINE
| ID: mdl-16299040
ABSTRACT
BACKGROUND AND AIMS:
Monocyte chemoattractant protein 1 (MCP-1) is increased transmurally in inflammatory bowel disease (IBD). Although MCP-1 is considered to play an important role in fibrotic disease in other organs, the role of MCP-1 in gut fibrosis is unknown. We investigated the fibrotic potential of MCP-1 in the gut by overexpressing this chemokine in the mouse colorectal wall.METHODS:
Intramural gene transfer by direct injection of adenovector into the mouse rectal wall was established. C57BL/6 and Rag2(-/-) (B and T cell deficient) mice received 2.5 x 10(9) plaque forming units of an adenovector encoding murine MCP-1 (AdMCP-1) or control virus (AdDL70) via intramural injection. Mice were killed at various time points and tissues were obtained for histopathological and biochemical analysis.RESULTS:
AdMCP-1 significantly increased collagen production in the colorectum and this was associated with significant elevation of transforming growth factor beta (TGF-beta) and tissue inhibitor of metalloproteinase (TIMP-1) protein. Transmural collagen deposition was observed after AdMCP-1 administration, and was accompanied by CD3+ T cells, F4/80+ macrophages, and vimentin+ cell infiltrates. Collagen was differentially distributed, with type I deposited in the muscularis mucosa and muscularis propria and type III in the submucosa and myenteric plexus. AdMCP-1 failed to induce collagen overproduction in immunodeficient Rag2(-/-) mice.CONCLUSION:
These findings suggest that MCP-1 can induce fibrosis in the gut and that this process involves interaction between T cells and vimentin positive fibroblasts/myofibroblasts, as well as the subsequent upregulation of TGF-beta and TIMP-1 production. This model provides a basis for considering MCP-1 in the pathogenesis of strictures in IBD.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Colon
/
Quimiocina CCL2
Tipo de estudio:
Prognostic_studies
Límite:
Animals
Idioma:
En
Revista:
Gut
Año:
2006
Tipo del documento:
Article
País de afiliación:
Canadá