Cigarette smoke extract induces expression of cell adhesion molecules in HUVEC via actin filament reorganization.
Epidemiologic studies have shown a strong association between cigarette smoking and cardiovascular diseases. Various oxidative species and free radicals are produced during cigarette smoking and these lead to endothelial dysfunction and inflammation. Expression of adhesion molecules, such as intercellular adhesion molecule-1 (ICAM-1), E-selectin, and vascular cell adhesion molecule-1, and adhesion of leukocytes are present in atherosclerosis. We showed previously that a nonfractionated cigarette smoke extract (CSE) induces surface expression of ICAM-1 and E-selectin in human umbilical vein endothelial cells (HUVEC). We then investigated the role of the MAPKs (ERK1/2, JNK, and p38) and AP-1 and the role of actin cytoskeleton reorganization in the CSE-induced expression of ICAM-1 and E-selectin. Western blot analysis showed that CSE treatment rapidly and significantly caused phosphorylation of JNK and ERK1/2 but not of p38. Cytochalasin D (an actin filament disruptor) partially inhibited CSE-induced ICAM-1 and E-selectin surface expression. However, inhibitors of ERK1/2 (PD98059) and JNK (SP600125) did not attenuate the CSE-induced ICAM-1 and E-selectin surface expression. The results of electrophoretic mobility shift assay showed that CSE enhanced AP-1 binding activity. Therefore, CSE activated AP-1 and upregulated ICAM-1 and E-selectin surface expression in HUVEC seem to be via an MAPK-independent pathway. Moreover, the dynamic reorganization of the actin cytoskeleton seems to be required for the CSE-induced surface expression of ICAM-1 and E-selectin.
Chen
Haw-Wen
HW
Department of Nutrition, China Medical University, Taichung, Taiwan.
Lii
Chong-Kuei
CK
Ku
Hua-Jung
HJ
Wang
Tsu-Shing
TS
D008841:Actin Cytoskeleton / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D015153:Blotting, Western; D018929:Cell Culture Techniques; D002460:Cell Line; D019040:E-Selectin / Q000096:biosynthesis; D004591:Electrophoresis, Polyacrylamide Gel; D024202:Electrophoretic Mobility Shift Assay; D042783:Endothelial Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000096:biosynthesis*; D014026:Nicotiana / Q000737:chemistry / Q000633:toxicity; D014028:Tobacco Smoke Pollution / Q000009:adverse effects*
D019040:E-Selectin; D014028:Tobacco Smoke Pollution; D018799:Intercellular Adhesion Molecule-1