Interleukin-6 reduces paraoxonase-1 activity in a dose-dependent manner; evidence for a potential novel lipoprotein-based modulatory mechanism

• Published in: Atherosclerosis 2016-09, Vol.252, p.e113-e114
• Main Authors: Abedpour Dehkordi, A, Nayeri, H, Naderi, G.A, Jafari Dinani, N, Boshtam, M
• Format: Article
• Language: English
• Subjects: Cardiovascular
• ISSN: 0021-9150; 1879-1484; 1879-1484
• DOI: 10.1016/j.atherosclerosis.2016.07.616

Objectives: The anti-oxidant/anti-inflammatory nature of HDL is mainly associated with paraoxonase-1 (PON1). Previous studies have revealed an inverse correlation between Interleukin-6 (IL-6) and PON1 expression. The current study investigates the effect of IL-6 on serum PON1 activity in vitro, given the potential structural capability of PON1 to host multiple ligands. Methods: PON1 activity was measured spectrophotometrically (234 nm) using paraoxon substrate in the presence of concentrations of IL-6 than control samples. A sequence alignment using the FASTA sequence was manually conducted to identify possible homologies between PON1 and the IL-6-binding protein. Statistical analysis was conducted using GraphPad Prism v5.0. Results: PON1 enzyme activity decreased by 15%, 26% (P<0.05) and 55% (P<0.001) in the presence of 4, 10 and 20 pg/ml of IL-6, respectively. in comparison with the controls. Student t. test was used as statistical method (p<0.05: statistically significant). There are potential homologies between PON1 active sites and know IL-6-binding residues. Conclusions: This study shows that IL-6 directly reduce the PON1 activity in a dose-dependent manner. This observation supports some studies indicating inverse correlation between PON1 and IL-6. However, as opposed to the gene-mediated approach, this study suggest that IL-6 may act directly through specific binding to PON1 (biochemical modulation). X ray crystallography can further scrutinize the present finding.