The correlation between proinflammatory cytokines, MAdCAM-1 and cellular infiltration in the inflamed colon from TNF-alpha gene knockout mice.
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.
Xu
Yinghua
Y
Discipline of Pathology, Bosch Institute, School of Medical Sciences, University of Sydney, Sydney, New South Wales, Australia.
Hunt
Nicholas H
NH
Bao
Shisan
S
D000818:Animals; D015815:Cell Adhesion Molecules / Q000276:immunology*; D002465:Cell Movement; D003092:Colitis / Q000139:chemically induced / Q000276:immunology*; D016207:Cytokines / Q000276:immunology*; D016264:Dextran Sulfate; D004198:Disease Susceptibility; D007070:Immunoglobulin A / Q000276:immunology; D007074:Immunoglobulin G / Q000276:immunology; D018836:Inflammation Mediators / Q000276:immunology*; D008264:Macrophages / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009088:Mucoproteins; D009504:Neutrophils / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000172:deficiency*; D015431:Weight Loss
D015815:Cell Adhesion Molecules; D016207:Cytokines; D007070:Immunoglobulin A; D007074:Immunoglobulin G; D018836:Inflammation Mediators; C489082:Madcam1 protein, mouse; D009088:Mucoproteins; D014409:Tumor Necrosis Factor-alpha; D016264:Dextran Sulfate