Impaired Resolution of Inflammation in the Endoglin Heterozygous Mouse Model of Chronic Colitis

Endoglin is a coreceptor of the TGF-β superfamily predominantly expressed on the vascular endothelium and selective subsets of immune cells. We previously demonstrated that Endoglin heterozygous (Eng+/−) mice subjected to dextran sulfate sodium (DSS) developed persistent gut inflammation and patholo...

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Main Authors: Madonna R. Peter (Author), Mirjana Jerkic (Author), Valentin Sotov (Author), David N. Douda (Author), Daniela S. Ardelean (Author), Niousha Ghamami (Author), Flavia Lakschevitz (Author), Meraj A. Khan (Author), Susan J. Robertson (Author), Michael Glogauer (Author), Dana J. Philpott (Author), Nades Palaniyar (Author), Michelle Letarte (Author)
Format: Book
Published: Hindawi Limited, 2014-01-01T00:00:00Z.
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Summary:Endoglin is a coreceptor of the TGF-β superfamily predominantly expressed on the vascular endothelium and selective subsets of immune cells. We previously demonstrated that Endoglin heterozygous (Eng+/−) mice subjected to dextran sulfate sodium (DSS) developed persistent gut inflammation and pathological angiogenesis. We now report that colitic Eng+/− mice have low colonic levels of active TGF-β1, which was associated with reduced expression of thrombospondin-1, an angiostatic factor known to activate TGF-β1. We also demonstrate dysregulated expression of BMPER and follistatin, which are extracellular regulators of the TGF-β superfamily that modulate angiogenesis and inflammation. Heightened colonic levels of the neutrophil chemoattractant and proangiogenic factor, CXCL1, were also observed in DSS-treated Eng+/− mice. Interestingly, despite increased macrophage and neutrophil infiltration, a gut-specific reduction in expression of the key phagocytic respiratory burst enzymes, NADPH oxidase 2 (Nox-2) and myeloperoxidase, was seen in Eng+/− mice undergoing persistent inflammation. Taken together, these findings suggest that endoglin is required for TGF-β superfamily mediated resolution of inflammation and fully functional myeloid cells.
Item Description:0962-9351
1466-1861
10.1155/2014/767185