Gp91(phox) contributes to the development of experimental inflammatory bowel disease.

Abstract

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.

• Authors: Shisan Bao, Emma D J Carr, Ying-Hua Xu, Nicholas H Hunt
• Journal: Immunology and cell biology (Immunol Cell Biol) Vol. 89 Issue 8 Pg. 853-60 (Nov 2011) ISSN: 1440-1711 [Electronic] United States
• PMID: 21321580 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Interleukin-6
• Membrane Glycoproteins
• Interleukin-10
• Dextran Sulfate
• Cybb protein, mouse
• NADPH Oxidase 2
• NADPH Oxidases
• neutrophil cytosolic factor 1

Topics

• Animals
• Colon (immunology, metabolism, pathology)
• Dextran Sulfate
• Endothelium, Vascular (immunology, pathology)
• Inflammation
• Inflammatory Bowel Diseases (chemically induced, immunology, metabolism, pathology)
• Interleukin-10 (biosynthesis)
• Interleukin-6 (biosynthesis)
• Intestinal Mucosa (metabolism)
• Intestines (immunology, pathology)
• Membrane Glycoproteins (genetics, metabolism)
• Mice
• Mice, Inbred C57BL
• Mice, Knockout
• NADPH Oxidase 2
• NADPH Oxidases (genetics, metabolism)
• Neutrophils (physiology)
• Respiratory Burst