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- Title
Aspirin Action in Endothelial Cells: Different Patterns of Response Between Chemokine CX3CL1/CX3CR1 and TNF-α/TNFR1 Signaling Pathways.
- Authors
Szukiewicz, Dariusz; Wojciechowska, Malgorzata; Bilska, Anna; Stangret, Aleksandra; Szewczyk, Grzegorz; Mittal, Tarun; Watroba, Mateusz; Kochanowski, Jan
- Abstract
Purpose: TNF-α induces fractalkine (CX3CL1) and its receptor CX3CR1 in endothelial cells through NF-қB activation. NF-қB inhibitors may reduce the expression of CX3CL1, and modulation of the CX3CL1/CX3CR1 signaling was proposed as a new target for aspirin. We examined the effects of aspirin on CX3CL1 and TNF-α production, as well as CX3CR1 and TNFR1 expression. Methods: HUVECs isolated after term pregnancies ( N = 28) were cultured in vitro. Lipopolysaccharide (1 μg/ml) was used as CX3CL1 inducer. HUVECs were exposed to six different concentrations of aspirin (between 1.0 and 6.0 mM) during 7 days. The levels of CX3CL1 and TNF-α in the culture media were measured using ELISA. After termination of the cultures, mean expressions of CX3CR1 and TNFR1 were examined in the immunostained paraffin sections using quantitative immunohistochemistry. Results: Aspirin significantly ( p < 0.05) decreased CX3CL1 production, and the mean decrease in CX3CL1 production was inversely proportional to increased ( p < 0.05) expression of CX3CR1. The combined mean CX3CL1 concentrations, including all time points, equaled 782.18 ± 74.4 pg/ml in aspirin treated HUVECs compared to a total concentration of 2467.53 ± 127.5 pg/ml combined from the respective time points in the controls. An inhibition of TNF-α production in HUVECs after pretreatment with aspirin was observed. Unlike in the case of CX3CR1 expression, there were no signs of TNFR1 upregulation. Conclusions: Autoregulation between CX3CL1 and CX3CR1 may explain overexpression of CX3CR1 as the compensatory effect in aspirin-treated HUVECs. Inhibition of CX3CR1 could prevent thrombotic complications in the early period after discontinuation of aspirin.
- Subjects
ASPIRIN; ENDOTHELIAL cells; CHEMOKINES; LIPOPOLYSACCHARIDES; GENETIC overexpression
- Publication
Cardiovascular Drugs & Therapy, 2015, Vol 29, Issue 3, p219
- ISSN
0920-3206
- Publication type
Article
- DOI
10.1007/s10557-015-6589-2