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Gremlin-1 inhibits macrophage migration inhibitory factor-dependent monocyte function and survival.
- Source :
-
International Journal of Cardiology . Oct2014, Vol. 176 Issue 3, p923-929. 7p. - Publication Year :
- 2014
-
Abstract
- Background Monocyte migration and their differentiation into macrophages critically regulate vascular inflammation and atherogenesis and are governed by macrophage migration inhibitory factor (MIF). Gremlin-1 binds to MIF. Current experimental evidences present Gremlin-1 as a potential physiological agent that might counter-regulate the inflammatory attributes of MIF. Methods and results We found that Gremlin-1 inhibited MIF-dependent monocyte migration and adhesion to activated endothelial cells in flow chamber perfusion assay in vitro and to the injured carotid artery of WT and ApoE-/- mice in vivo as deciphered by intravital microscopy. Intravenous administration of Gremlin-1, but not of control protein, significantly reduced leukocyte recruitment towards the inflamed carotid artery of ApoE-/- mice. Besides, leukocytes from MIF-/- when administered into ApoE-/- mice showed lesser adhesion as compared to wild type. In the presence of Gremlin-1 however, adhesion of wild type, but not of MIF-/- leukocytes, to the carotid artery was significantly inhibited as compared to control. Gremlin-1 also inhibited the MIF-induced differentiation of monocytes into macrophages. Gremlin-1 substantially inhibited the anti-apoptotic impact of MIF on monocytes against BH3 mimetic ABT-737-induced apoptosis as verified by Annexin V-binding, caspase 3 activity, and mitochondrial depolarization. Conclusions Therefore Gremlin-1 can modulate MIF dependent monocyte adhesion, migration, differentiation and survival. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 01675273
- Volume :
- 176
- Issue :
- 3
- Database :
- Academic Search Index
- Journal :
- International Journal of Cardiology
- Publication Type :
- Academic Journal
- Accession number :
- 98792466
- Full Text :
- https://doi.org/10.1016/j.ijcard.2014.08.051