title: Glucagon-like peptide-1(1-37) inhibits chemokine-induced migration of human CD4-positive lymphocytes.
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.
authors.affiliation: Department of Internal Medicine I-Cardiology, University of Aachen, Pauwelstr. 30, Aachen, Germany. nmarx@ukaachen.de
authors.forename: Nikolaus
authors.initials: N
authors.lastname: Marx
authors.forename: Mathias
authors.initials: M
authors.lastname: Burgmaier
authors.forename: Philipp
authors.initials: P
authors.lastname: Heinz
authors.forename: Mirjam
authors.initials: M
authors.lastname: Ostertag
authors.forename: Angelina
authors.initials: A
authors.lastname: Hausauer
authors.forename: Helga
authors.initials: H
authors.lastname: Bach
authors.forename: Renate
authors.initials: R
authors.lastname: Durst
authors.forename: Vinzenz
authors.initials: V
authors.lastname: Hombach
authors.forename: Daniel
authors.initials: D
authors.lastname: Walcher
mesh_terms: 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
chemical_list: 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