α7 nicotine acetylcholine receptor inhibits lipopolysaccharide-inducedintercellular adhesion molecule-1 expression in endothelial cells

Abstract

Objective To investigate the effects of α7 nicotine acetylcholine receptor (α7nAChR) on lipopolysaccharide (LPS)-induced expressions of intercellular adhesion molecule-1 (ICAM-1) in human umbilical vein endothelial cells. Methods Human umbilical vein endothelial cell line EVC-304 were cultured and treated with LPS, and the expressions of ICAM-1 and α7nAChR were detected by reverse transcriptase-polymerase chain reaction (RT-PCR) and Western blotting. Then cells were treated with LPS, LPS+ GTS-21 and LPS+ α-bungarotoxin (α-BTX) separately. Expressions of ICAM-1 and phosphorylated p38 Mitogen-activated protein kinase (p-p38) were determined by Western blotting. Finally, cells were pretreated with p38MAPK inhibitor SB203580, and the expressions of ICAM-1 were determined. Results LPS could significantly increase the expressions of α7nAChR in endothelial cells (14.70±2.08 vs. 3.93±1.01, P=0.002; 0.40±0.08 vs. 0.17±0.04, P=0.008). LPS stimulation could promote expressions of ICAM-1 (6.65±0.21 vs. 2.00±0.29, P=0.029; 0.78±0.04 vs. 0.58±0.11, P=0.032) and p38 phosphorylation (0.73±0.08 vs. 0.29±0.06, P=0.008) which could be could be attenuated by activation of α7nAChR (p-p38: 0.49±0.09 vs. 0.73±0.08, P=0.008, ICAM-1: 0.42±0.07 vs. 0.17±0.06, P=0.002), and this inhibitory effect could be relieved by α7nAChR antagonist (p-p38: 0.80±0.10 vs. 0.73±0.08, P=0.310, ICAM-1: 0.42±0.07 vs. 0.76±0.13, P=0.002). The expressions of ICAM-1 also could be restraint by the treatment of p38MAPK inhibitor (0.55±0.10 vs. 0.82±0.08, P=0.001). Conclusion LPS could marked increase the expressions of α7nAChR and ICAM-1. Activation of α7nAChR could reduce expressions of ICAM-1 by suppression the activation of p38MAPK pathway. Key words: α7 nicotinic acetylcholine receptor; Lipopolysaccharide; Endothelial cells; Intercellular adhesion molecule-1; P38 Mitogen-activated protein kinase