Homocysteine up-regulates vascular transmembrane chemokine CXCL16 and induces CXCR6+ lymphocyte recruitment in vitro and in vivo

Journal of Cellular and Molecular Medicine
O PosteaAndreas Ludwig

Abstract

Hyperhomocysteinemia induces endothelial dysfunction and promotes atherosclerotic vascular disease. Infiltrates of activated macrophages and lymphocytes are observed in human and experimental atherosclerotic lesions, their emigration being guided by endothelial-leukocyte adhesion molecules and chemoattractants. The CXC-chemokine CXCL16 functions as an adhesion molecule by interacting with its receptor (CXCR6) and also as a scavenger for oxidized low density lipoprotein (oxLDL). We investigated the modulation of CXCL16 on cultured endothelial cells (EC) and the recruitment of CXCR6(+) lymphocytes in response to homocysteine (Hcy), in vitro and in vivo. Hcy-stimulated EC show a significant increase in CXCL16 mRNA and protein expression. Incubation of EC with d,l-Hcy and l-Hcy significantly increased CXCR6(+) lymphocyte adhesion to EC while l-Cysteine (l-Cys) had no effect. Furthermore, EC stimulation with Hcy increased uptake of DiI-oxLDL. An anti-CXCL16 monoclonal antibody, antioxidants (Tiron) and PPAR-gamma agonists (Pioglitazone) considerably reduced CXCR6(+) lymphocyte adhesion and uptake of DiI-oxLDL. Upon injection in the peritoneal cavities of mice, l-Hcy and not l-Cys, increased the number of CXCR6(+) lymphocytes, which ...Continue Reading

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Citations

Nov 1, 2011·EMBO Molecular Medicine·Rory R Koenen, Christian Weber
Oct 27, 2015·Journal of Cellular and Molecular Medicine·Daniela DreymuellerChristian Stoppe
Apr 20, 2013·Journal of Molecular and Cellular Cardiology·Hasan OralElisa A Liehn
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Mar 3, 2012·Arteriosclerosis, Thrombosis, and Vascular Biology·Otilia PosteaRory R Koenen
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Aug 1, 2020·Cellular and Molecular Life Sciences : CMLS·Yutong MiaoJuan Feng
May 14, 2009·The American Journal of Pathology·Paul GutweinJosef Pfeilschifter

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Methods Mentioned

BETA
PCR
FACS
lavage
flow cytometry
ELISA
nuclear translocation

Software Mentioned

CellQuest

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