Volume 18, No 12, Dec 2008

ISSN: 1001-0602 
EISSN: 1748-7838 2018 
impact factor 17.848* 
(Clarivate Analytics, 2019)

Volume 18 Issue 12, December 2008: 1220-1229

ORIGINAL ARTICLES

The role of granulocyte macrophage-colony-stimulating factor in acute intestinal inflammation

Yinghua Xu, Nicholas H Hunt and Shisan Bao

Department of Pathology (D06), Bosch Institute, School of Medical Sciences, University of Sydney, New South Wales 2006, Australia Correspondence: Shisan Bao,(bobbao@med.usyd.edu.au)

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-α 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-γ 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.

Cell Research (2008) 18:1220-1229. doi: 10.1038/cr.2008.310; published online 25 November 2008

FULL TEXT | PDF

Browse 1711