In:
Journal of Leukocyte Biology, Oxford University Press (OUP), Vol. 76, No. 6 ( 2004-08-31), p. 1111-1117
Abstract:
Breakdown of normal mucosal immunity is one of the major causes for inflammatory bowel disease. Interleukin (IL)-6 is a proinflammatory cytokine produced aberrantly in various types of inflammation, but its role in inflammatory bowel disease is still obscure. Hence, we analyzed the roles of IL-6 in the pathogenesis of murine T cell transfer colitis, whose histopathology resembles Crohn's disease. The transfer of CD4+CD45RBhigh T cells into severe combined immunodeficiency mice induced the infiltration of T cells and macrophages, and the gene expression of CC chemokine receptor (CCR)1, CCR2, CCR5, CXC chemokine receptor 3, their ligands, tumor necrosis factor-α, interferon-γ, and IL-6 was progressively augmented as colitis developed. The incidence of transmural colitis was significantly reduced with a minimal decrease in the severity of colitis in recipients transferred with CD4+CD45RBhigh T cells derived from IL-6-deficient mice compared with those with wild-type mice. Moreover, the gene expression of several cytokines, chemokines, and matrix metalloproteinases was reduced significantly in recipients transferred with IL-6-deficient, mice-derived T cells. These observations suggested that T cell-derived IL-6 may augment the gene expression of several proinflammatory molecules, thereby causing transmural inflammation. Thus, IL-6 might be a promising target for treating transmural inflammation in Crohn's disease, which can lead to severe complications such as strictures, fissures, and fistulas.
Type of Medium:
Online Resource
ISSN:
0741-5400
,
1938-3673
Language:
English
Publisher:
Oxford University Press (OUP)
Publication Date:
2004
detail.hit.zdb_id:
2026833-6
SSG:
12
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