Impaired resolution of inflammation in the Endoglin heterozygous mouse model of chronic colitis.

Abstract

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.

• Authors: Madonna R Peter, Mirjana Jerkic, Valentin Sotov, David N Douda, Daniela S Ardelean, Niousha Ghamami, Flavia Lakschevitz, Meraj A Khan, Susan J Robertson, Michael Glogauer, Dana J Philpott, Nades Palaniyar, Michelle Letarte
• Journal: Mediators of inflammation (Mediators Inflamm) Vol. 2014 Pg. 767185 ( 2014) ISSN: 1466-1861 [Electronic] United States
• PMID: 25114380 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Chemokine CXCL1
• Endoglin
• Eng protein, mouse
• Intracellular Signaling Peptides and Proteins
• Transforming Growth Factor beta1

Topics

• Animals
• Chemokine CXCL1 (metabolism)
• Colitis (genetics, metabolism)
• Disease Models, Animal
• Endoglin
• Heterozygote
• Inflammation (genetics, metabolism)
• Intracellular Signaling Peptides and Proteins (genetics, metabolism)
• Mice
• Mice, Inbred C57BL
• Signal Transduction (genetics, physiology)
• Transforming Growth Factor beta1 (genetics, metabolism)