First Author | Xu Y | Year | 2007 |
Journal | Immunol Cell Biol | Volume | 85 |
Issue | 8 | Pages | 633-9 |
PubMed ID | 17768420 | Mgi Jnum | J:128018 |
Mgi Id | MGI:3765373 | Doi | 10.1038/sj.icb.7100112 |
Citation | Xu Y, et al. (2007) The correlation between proinflammatory cytokines, MAdCAM-1 and cellular infiltration in the inflamed colon from TNF-alpha gene knockout mice. Immunol Cell Biol 85(8):633-9 |
abstractText | Tumour necrosis factor (TNF) is important in the development of inflammatory bowel disease. TNF-alpha-deficient mice show more severe colonic inflammation than wild-type (Wt) mice, but the underlying mechanism remains unclear. Using immunohistochemistry, enzyme-linked-immunosorbent assay and histopathology, we found that there was a higher level of macrophage infiltration in TNF-alpha(-/-) compared to Wt mice. This is consistent with higher levels of monocyte chemotactic protein-1, interleukin (IL)-6 and granulocyte monocyte colony-stimulating factor (GM-CSF) in the inflamed colon from the TNF-alpha(-/-) mice, compared to the Wt mice, following dextran sulphate sodium (DSS) challenge. There was close correlation between clinical observations and histopathological findings in both Wt and TNF-alpha(-/-) mice. The expression of mucosal addressin cell adhesion molecule 1 (MAdCAM-1) was upregulated in the colon of Wt and TNF-alpha(-/-) mice following DSS challenge. Interestingly, the induction of MAdCAM-1 was relatively lower in the inflamed colon of TNF-alpha(-/-) mice, despite the higher inflammatory cell infiltrate, compared to their Wt counterparts. On the other hand, TNF-alpha(-/-) mice had significantly lower baseline levels of colonic IL-4, IL-6 and GM-CSF. Furthermore, there was a reduction of both immunoglobulin A (IgA) and IgG in the gut from TNF-alpha(-/-) mice following DSS challenge. These data indicate that TNF-alpha deficiency alters homoeostasis of the colonic chemokine/cytokine environment and humoral immune response, resulting in an exacerbation of acute DSS-induced colitis in TNF-alpha(-/-) mice. These findings support the idea that TNF-alpha plays a role in the acute stage of intestinal inflammation.Immunology and Cell Biology (2007) 85, 633-639; doi:10.1038/sj.icb.7100112; published online 4 September 2007. |