Wu, X.; Xu, M.; Liu, Y.; Luo, S.; Zheng, X.; Xu, S.; Weng, J. Dual Pharmacological Inhibition of IRAK1 and IRAK4 Prevents LPS Induced Monocyte Adhesion to Endothelial Cells. Preprints2021, 2021050579. https://doi.org/10.20944/preprints202105.0579.v1
APA Style
Wu, X., Xu, M., Liu, Y., Luo, S., Zheng, X., Xu, S., & Weng, J. (2021). Dual Pharmacological Inhibition of IRAK1 and IRAK4 Prevents LPS Induced Monocyte Adhesion to Endothelial Cells. Preprints. https://doi.org/10.20944/preprints202105.0579.v1
Chicago/Turabian Style
Wu, X., Suowen Xu and Jianping Weng. 2021 "Dual Pharmacological Inhibition of IRAK1 and IRAK4 Prevents LPS Induced Monocyte Adhesion to Endothelial Cells" Preprints. https://doi.org/10.20944/preprints202105.0579.v1
Abstract
Inflammation associated endothelial dysfunction represents a pivotal contributor to atherosclerosis. Increasingly evidence has demonstrated that interleukin 1 receptor (IL1-R) / toll-like receptor (TLR) signaling participated in the development of atherosclerosis. Previous studies indicated the therapeutic potential of anti-inflammatory therapy in anti-atherosclerosis. The present study examined the effect of IL-1R-associated kinase 1 and 4 inhibitors (IRAK1/4i) in regulating endothelial dysfunction. IRAK1/4i showed little endothelial toxicity at concentrations from 1 to 10 μM. Inhibition of IRAK1/4 alleviated endothelial activation induced by LPS in vitro evidenced by attenuated monocyte adhesion to the endothelium. Mechanistically, blockade of IRAK1/4 ameliorated the transcriptional activity of NF-κB. Taken together, our findings demonstrated that dual inhibition of IRAK1 and IRAK4 attenuates endothelial dysfunction, suggesting pharmaceutical inhibition of IRAK1/4 might be a potential strategy to combat endothelial dysfunction and atherosclerosis.
Medicine and Pharmacology, Cardiac and Cardiovascular Systems
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