Early bacterial dependent induction of inducible nitric oxide synthase (iNOS) in epithelial cells upon transfer of CD45RBhigh CD4+ T cells in a model for experimental colitis
✍ Scribed by Gerard Dijkstra; Saravanan Yuvaraj; Han-Qing Jiang; Judy C.A.M. Bun; Han Moshage; Natasha Kushnir; Maikel P. Peppelenbosch; John J. Cebra; Nicolaas A. Bos
- Publisher
- John Wiley and Sons
- Year
- 2007
- Tongue
- English
- Weight
- 582 KB
- Volume
- 13
- Category
- Article
- ISSN
- 1078-0998
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✦ Synopsis
Background:
Both the role of inducible nitric oxide synthase (inos) in the development of inflammatory bowel disease (ibd) as well as the molecular details governing its mucosal induction remain unclear.
Methods:
In the present study we evaluated the role of the residing intestinal microflora in the induction of epithelial inos upon transfer of cd45rb(high) cd4(+) t cells to scid mice. cb-17 scid mice were reared with conventional flora (cnv) or germfree cb-17 scid mice were monoassociated with helicobacter muridarum, act a(-) mutant listeria monocytogenes, segmented filamentous bacteria (sfb), or ochrobactrum anthropi.
Results:
Within 2 weeks cnv scid mice injected with cd45rb(high) cd4(+) t cells showed a focal, epithelial inos expression on the apical site of villi that preceded the infiltration of cd4(+) t cells and cytokine production followed by extension of this expression to the entire surface along the whole crypt axis as the colitis progressed. scid mice monoassociated with h. muridarum developed a severe colitis and showed high epithelial inos expression. cnv-scid mice without t cells and scid mice monoassociated with sfb did not show any inos expression, whereas scid mice monoassociated with act a(-) mutant l. monocytogenes and o. anthropi showed some scattered epithelial inos staining on the apical site of a few villi, but none of these mice developed colitis.
Conclusions:
These findings demonstrate that the expression of epithelial inos is highly bacterium-specific and correlates with the severity of disease, suggesting an important role for this enzyme in the development of ibd.