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Different Responses in CX3CL1/CX3CR1 and TNF‐α/TNFRSF1A Signaling Pathways to Aspirin in Human Umbilical Vein Endothelial Cells (HUVECs)
Author(s) -
Szukiewicz Dariusz,
Stangret Aleksandra
Publication year - 2015
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.29.1_supplement.625.5
Subject(s) - cx3cr1 , cx3cl1 , aspirin , umbilical vein , tumor necrosis factor alpha , chemokine , pharmacology , medicine , receptor , chemistry , immunology , in vitro , biochemistry , chemokine receptor
Antiprostaglandin and antiplatelet actions of aspirin related to non‐equal and irreversible inhibition of cyclooxygenases (COX1, COX2) are widely known. COX‐independent antiinflammatory effects of aspirin were also reported. Acting as the nuclear factor‐kB (NF‐kB)inhibitor on endothelial cells, aspirin may modulate chemokine fractalkine (CX3CL1) signaling through its sole receptor CX3CR1. Thus, aspirin may reveal the opposite effect to TNF‐α, a strong inducer of CX3CL1/CX3CR1 signaling. We examined the effects of aspirin on CX3CL1 and TNF‐α production, as well as CX3CR1 and TNFRSF1A expression. HUVECs were isolated after normal term pregnancies (N = 24) and cultured in vitro. The cultures were exposed to aspirin (dose range: 1.0 – 6.0 mM) during the 7 day period. The mean concentrations of CX3CL1 and TNF‐α in the culture media supernatants were assessed at predefined time points by ELISA. After termination of the cultures, CX3CR1 and TNFRSF1A were immunostained in formalin fixed and paraffin embedded sections. To estimate the mean expression of these receptors, quantitative immunohistochemistry was applied. Aspirin significantly (p < 0.05) reduced production of CX3CL1, and the mean decline in CX3CL1 production was inversely proportional to the significantly (p < 0.05) augmented expression of CX3CR1. An inhibition of TNF‐α synthesis in HUVECs in response to aspirin treatment was also reported. There were no signs indicating upregulation of TNFRSF1A. Since autoregulatory relationships between CX3CL1 and CX3CR1 were proposed, overexpression of CX3CR1 observed in aspirin‐treated HUVECs may be a form of compensatory mechanism. WUM grant: 2M2‐N‐14