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Cell Mol Life Sci. 2010 Oct;67(20):3549-55. doi: 10.1007/s00018-010-0396-5. Epub 2010 May 21.

Glucagon-like peptide-1(1-37) inhibits chemokine-induced migration of human CD4-positive lymphocytes.

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1
Department of Internal Medicine I-Cardiology, University of Aachen, Pauwelstr. 30, Aachen, Germany. nmarx@ukaachen.de

Abstract

The present study examined the effect of GLP-1(1-37) on chemokine-induced CD4-positive lymphocyte migration as an early and critical step in atherogenesis. Pretreatment with GLP-1(1-37) reduced the SDF-induced migration of isolated human CD4-positive lymphocytes in a concentration-dependent manner. Similar effects were seen when RANTES was used as a chemokine. GLP-1(1-37)'s effect on CD4-positive lymphocyte migration was mediated through an early inhibition of chemokine-induced PI-3 kinase activity. Downstream, GLP-1(1-37) inhibited SDF-induced phosphorylation of MLC and cofilin and limited f-actin formation as well as ICAM3 translocation. Furthermore, exendin-4 inhibited SDF-induced migration of CD4-positive lymphocytes similarly to GLP-1(1-37), and transfection of these cells with GLP-1 receptor siRNA abolished GLP-1(1-37)'s action on chemokine-induced ICAM3 translocation, suggesting an effect mediated via the GLP-1 receptor. Thus, GLP-1(1-37) inhibits chemokine-induced CD4-positive lymphocyte migration by inhibition of the PI3-kinase pathway and via the GLP-1 receptor. This effect provides a potential novel mechanism for how GLP-1(1-37) may modulate vascular disease.

PMID:
20495843
DOI:
10.1007/s00018-010-0396-5
[Indexed for MEDLINE]
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