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Gp91 phox contributes to the development of experimental inflammatory bowel disease
Author(s) -
Bao Shisan,
Carr Emma DJ,
Xu YingHua,
Hunt Nicholas H
Publication year - 2011
Publication title -
immunology and cell biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.999
H-Index - 104
eISSN - 1440-1711
pISSN - 0818-9641
DOI - 10.1038/icb.2011.4
Subject(s) - colitis , myeloperoxidase , nadph oxidase , inflammatory bowel disease , immunology , inflammation , knockout mouse , respiratory burst , chemistry , phagocyte , medicine , immune system , oxidative stress , disease , receptor
Inflammatory bowel disease (IBD) is related to dysfunction of intestinal immunity. Neutrophils have an important role in innate immunity via the oxidative burst, using the p47phox‐ and gp91 phox ‐containing NAD(P)H oxidase known as Nox2. In dextran sulphate sodium (DSS)‐induced colitis, no significant difference in inflammation between p47 phox −/− and wild‐type (WT) mice was reported, but there was improved endothelium‐dependent arteriolar dilation in gp91 phox−/− mice, compared with that in WT mice. Gp91 phox and p47 phox are not only essential components of phagocyte Nox2, but also have roles in other enzymes. Thus the differences in response of their respective gene knockout mice to DSS challenge are not completely unexpected, but need further investigation. The clinicopathological changes and immunological responses to DSS challenge have not been fully described in gp91 phox−/− mice. Thus we treated WT and gp91 phox−/− mice with 2.5% DSS for 7 days. The gp91 phox−/− mice developed less severe colitis than WT mice following DSS treatment, reflected by a smaller body weight loss, less rectal bleeding and fewer histopathological changes. Less colonic myeloperoxidase was observed in gp91 phox−/− , compared with WT mice, following DSS challenge, correlating with interleukin (IL)‐6 production. IL‐10 was upregulated in both gp91 phox−/− and WT mice, but was significantly higher in the latter, following 7 days DSS challenge. These results suggest that gp91 phox−/− mice are less susceptible to acute DSS‐induced colitis, possibly because of a reduced oxidative burst in the intestine and, consequently, less tissue damage.