caa a22 4500 606158421 CHVBK 20210128100619.0 cr unu---uuuuu 210128e20150601xx s 000 0 eng 10.1007/s10557-015-6589-2 doi (NATIONALLICENCE)springer-10.1007/s10557-015-6589-2 Aspirin Action in Endothelial Cells: Different Patterns of Response Between Chemokine CX3CL1/CX3CR1 and TNF-α/TNFR1 Signaling Pathways [Elektronische Daten] [Dariusz Szukiewicz, Malgorzata Wojciechowska, Anna Bilska, Aleksandra Stangret, Grzegorz Szewczyk, Tarun Mittal, Mateusz Watroba, Jan Kochanowski] 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 (1μg/ml) was used as CX3CL1 inducer. HUVECs were exposed to six different concentrations of aspirin (between 1.0 and 6.0mM) during 7days. 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 ± 74.4pg/ml in aspirin treated HUVECs compared to a total concentration of 2467.53 ± 127.5pg/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. The Author(s), 2015 Aspirin nationallicence Endothelial cells nationallicence Fractalkine nationallicence CX3CR1 nationallicence TNF-α nationallicence TNFR1 nationallicence Szukiewicz Dariusz Department of General & Experimental Pathology with Centre for Preclinical Research and Technology (CEPT), Medical University of Warsaw, ul. Pawinskiego 3C, 02-106, Warsaw, Poland aut Wojciechowska Malgorzata Department of General & Experimental Pathology with Centre for Preclinical Research and Technology (CEPT), Medical University of Warsaw, ul. Pawinskiego 3C, 02-106, Warsaw, Poland aut Bilska Anna Department of General & Experimental Pathology with Centre for Preclinical Research and Technology (CEPT), Medical University of Warsaw, ul. Pawinskiego 3C, 02-106, Warsaw, Poland aut Stangret Aleksandra Department of General & Experimental Pathology with Centre for Preclinical Research and Technology (CEPT), Medical University of Warsaw, ul. Pawinskiego 3C, 02-106, Warsaw, Poland aut Szewczyk Grzegorz Department of General & Experimental Pathology with Centre for Preclinical Research and Technology (CEPT), Medical University of Warsaw, ul. Pawinskiego 3C, 02-106, Warsaw, Poland aut Mittal Tarun Department of Obstetrics & Gynecology, Second Faculty of Medicine, Medical University of Warsaw, ul. Kondratowicza 8, 03-242, Warsaw, Poland aut Watroba Mateusz Department of General & Experimental Pathology with Centre for Preclinical Research and Technology (CEPT), Medical University of Warsaw, ul. Pawinskiego 3C, 02-106, Warsaw, Poland aut Kochanowski Jan Department of Neurology, Second Faculty of Medicine, Medical University of Warsaw, ul. Ceglowska 80, 01-809, Warsaw, Poland aut Cardiovascular Drugs and Therapy Springer US; http://www.springer-ny.com 29/3(2015-06-01), 219-229 0920-3206 29:3<219 2015 29 10557 https://doi.org/10.1007/s10557-015-6589-2 text/html Onlinezugriff via DOI BK010053 XK010053 XK010000 Metadata rights reserved Springer special CC-BY-NC licence nationallicence 1 research-article jats NATIONALLICENCE NATIONALLICENCE NL-springer NATIONALLICENCE 856 40 https://doi.org/10.1007/s10557-015-6589-2 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Szukiewicz Dariusz Department of General & Experimental Pathology with Centre for Preclinical Research and Technology (CEPT), Medical University of Warsaw, ul. Pawinskiego 3C, 02-106, Warsaw, Poland aut NATIONALLICENCE 700 1- Wojciechowska Malgorzata Department of General & Experimental Pathology with Centre for Preclinical Research and Technology (CEPT), Medical University of Warsaw, ul. Pawinskiego 3C, 02-106, Warsaw, Poland aut NATIONALLICENCE 700 1- Bilska Anna Department of General & Experimental Pathology with Centre for Preclinical Research and Technology (CEPT), Medical University of Warsaw, ul. Pawinskiego 3C, 02-106, Warsaw, Poland aut NATIONALLICENCE 700 1- Stangret Aleksandra Department of General & Experimental Pathology with Centre for Preclinical Research and Technology (CEPT), Medical University of Warsaw, ul. Pawinskiego 3C, 02-106, Warsaw, Poland aut NATIONALLICENCE 700 1- Szewczyk Grzegorz Department of General & Experimental Pathology with Centre for Preclinical Research and Technology (CEPT), Medical University of Warsaw, ul. Pawinskiego 3C, 02-106, Warsaw, Poland aut NATIONALLICENCE 700 1- Mittal Tarun Department of Obstetrics & Gynecology, Second Faculty of Medicine, Medical University of Warsaw, ul. Kondratowicza 8, 03-242, Warsaw, Poland aut NATIONALLICENCE 700 1- Watroba Mateusz Department of General & Experimental Pathology with Centre for Preclinical Research and Technology (CEPT), Medical University of Warsaw, ul. Pawinskiego 3C, 02-106, Warsaw, Poland aut NATIONALLICENCE 700 1- Kochanowski Jan Department of Neurology, Second Faculty of Medicine, Medical University of Warsaw, ul. Ceglowska 80, 01-809, Warsaw, Poland aut NATIONALLICENCE 773 0- Cardiovascular Drugs and Therapy Springer US; http://www.springer-ny.com 29/3(2015-06-01), 219-229 0920-3206 29:3<219 2015 29 10557