PMID- 19030026 OWN - NLM STAT- MEDLINE DCOM- 20081222 LR - 20210102 IS - 1748-7838 (Electronic) IS - 1001-0602 (Linking) VI - 18 IP - 12 DP - 2008 Dec TI - The role of granulocyte macrophage-colony-stimulating factor in acute intestinal inflammation. PG - 1220-9 LID - 10.1038/cr.2008.310 [doi] AB - 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. FAU - Xu, Yinghua AU - Xu Y AD - Department of Pathology (D06), Bosch Institute, School of Medical Sciences, University of Sydney, New South Wales 2006, Australia. FAU - Hunt, Nicholas H AU - Hunt NH FAU - Bao, Shisan AU - Bao S LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - England TA - Cell Res JT - Cell research JID - 9425763 RN - 0 (Cytokines) RN - 83869-56-1 (Granulocyte-Macrophage Colony-Stimulating Factor) RN - 9042-14-2 (Dextran Sulfate) SB - IM MH - Acute Disease MH - Animals MH - Colitis/*immunology/pathology MH - Cytokines/immunology MH - Dextran Sulfate MH - Granulocyte-Macrophage Colony-Stimulating Factor/*deficiency/*immunology MH - Immunohistochemistry MH - Inflammation/pathology MH - Inflammatory Bowel Diseases/*immunology/pathology MH - Intestines/microbiology/pathology MH - Mice MH - Mice, Knockout EDAT- 2008/11/26 09:00 MHDA- 2008/12/23 09:00 CRDT- 2008/11/26 09:00 PHST- 2008/11/26 09:00 [pubmed] PHST- 2008/12/23 09:00 [medline] PHST- 2008/11/26 09:00 [entrez] AID - cr2008310 [pii] AID - 10.1038/cr.2008.310 [doi] PST - ppublish SO - Cell Res. 2008 Dec;18(12):1220-9. doi: 10.1038/cr.2008.310.