期刊
CELLULAR AND MOLECULAR LIFE SCIENCES
卷 67, 期 20, 页码 3549-3555出版社
SPRINGER BASEL AG
DOI: 10.1007/s00018-010-0396-5
关键词
GLP-1; CD4-positive lymphocytes; Migration; Chemokines; Atherosclerosis
资金
- Deutsche Forschungsgemeinschaft [DFG-MA2047/4-1, DFG-WA 2145/1-1]
- Landesforschungsschwerpunkt Baden-Wurttemberg
- Novartisstiftung fur therapeutische Forschung
- Karl und Lore Klein-Stiftung
- Else-Kroner-Fresenius-Stiftung
- MSD
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.
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