Glucagon-like peptide-1(1-37) inhibits chemokine-induced migration of human CD4-positive lymphocytes.
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.
Marx
Nikolaus
N
Department of Internal Medicine I-Cardiology, University of Aachen, Pauwelstr. 30, Aachen, Germany. nmarx@ukaachen.de
Burgmaier
Mathias
M
Heinz
Philipp
P
Ostertag
Mirjam
M
Hausauer
Angelina
A
Bach
Helga
H
Durst
Renate
R
Hombach
Vinzenz
V
Walcher
Daniel
D
D051339:Actin Depolymerizing Factors / Q000378:metabolism; D000199:Actins / Q000378:metabolism; D015703:Antigens, CD / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology* / Q000187:drug effects* / Q000201:enzymology; D015815:Cell Adhesion Molecules / Q000378:metabolism; D002465:Cell Movement / Q000187:drug effects*; D054377:Chemokine CXCL12 / Q000494:pharmacology*; D004789:Enzyme Activation / Q000187:drug effects; D052216:Glucagon-Like Peptide 1 / Q000494:pharmacology*; D000067757:Glucagon-Like Peptide-1 Receptor; D006801:Humans; D018994:Myosin Light Chains / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D021381:Protein Transport / Q000187:drug effects; D034741:RNA, Small Interfering / Q000378:metabolism; D018027:Receptors, Glucagon / Q000378:metabolism; D014162:Transfection
D051339:Actin Depolymerizing Factors; D000199:Actins; D015703:Antigens, CD; D015815:Cell Adhesion Molecules; D054377:Chemokine CXCL12; C000593833:GLP1R protein, human; D000067757:Glucagon-Like Peptide-1 Receptor; C483616:ICAM3 protein, human; D018994:Myosin Light Chains; D034741:RNA, Small Interfering; D018027:Receptors, Glucagon; D052216:Glucagon-Like Peptide 1; D019869:Phosphatidylinositol 3-Kinases