Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

Dual Pharmacological Inhibition of IRAK1 and IRAK4 Prevents LPS Induced Monocyte Adhesion to Endothelial Cells

Version 1 : Received: 22 May 2021 / Approved: 24 May 2021 / Online: 24 May 2021 (15:09:08 CEST)

How to cite: 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. Preprints 2021, 2021050579 (doi: 10.20944/preprints202105.0579.v1). 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. Preprints 2021, 2021050579 (doi: 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.

Keywords

IRAK1; IRAK4; endothelial cells; inflammation; cardiovascular disease

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