The role of granulocyte macrophage-colony-stimulating factor in acute intestinal inflammation.
An imbalance of mucosal pro- and anti-inflammatory cytokines is crucial in the pathogenesis of inflammatory bowel disease (IBD). GM-CSF influences the development of hemopoietic cells. The precise role of GM-CSF in IBD remains to be elucidated. GM-CSF gene knockout (GM-CSF(-/-)) and wild-type (Wt) mice were challenged with 2.5% dextran sulfate sodium (DSS) for 7 days. The ensued clinical and pathological changes, macrophage infiltration, colonic cytokine production, and bacterial counts were examined. DSS-treated GM-CSF(-/-) mice developed more severe acute colitis than DSS-treated Wt mice, reflected by a greater body weight loss, more rectal bleeding, and aggravated histopathological changes. More infiltrating macrophages were observed in GM-CSF(-/-), compared with Wt mice following DSS challenge, correlating with monocyte chemoattractant protein-1 (MCP-1) production. The levels of colonic IL-17 and TNF-alpha were increased significantly in GM-CSF(-/-) mice, but not in Wt mice, following DSS administration. The level of IL-6 was increased by 1.5- and 2-fold in the colon of GM-CSF(-/-) and Wt mice, respectively, following DSS challenge. No significant changes in IL-4 and IFN-gamma were detected in Wt and GM-CSF(-/-) mice following DSS treatment. The bacteria recovery from colon was increased about 15- and 5-fold, respectively, in Wt mice and GM-CSF(-/-) mice following DSS challenge. These results suggest that GM-CSF(-/-) mice are more susceptible to acute DSS-induced colitis, possibly because of an impaired gut innate immune response as a result of diminished GM-CSF.
Xu
Yinghua
Y
Department of Pathology (D06), Bosch Institute, School of Medical Sciences, University of Sydney, New South Wales 2006, Australia.
Hunt
Nicholas H
NH
Bao
Shisan
S
D000208:Acute Disease; D000818:Animals; D003092:Colitis / Q000276:immunology* / Q000473:pathology; D016207:Cytokines / Q000276:immunology; D016264:Dextran Sulfate; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000172:deficiency* / Q000276:immunology*; D007150:Immunohistochemistry; D007249:Inflammation / Q000473:pathology; D015212:Inflammatory Bowel Diseases / Q000276:immunology* / Q000473:pathology; D007422:Intestines / Q000382:microbiology / Q000473:pathology; D051379:Mice; D018345:Mice, Knockout
D016207:Cytokines; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D016264:Dextran Sulfate