Document Type

Article

Publication Date

9-22-2016

DOI

http://dx.doi.org/10.1038/ncomms12823

Abstract

Endothelial dysfunction is a hallmark of systemic inflammatory response underlying multiple organ failure. Here we report a novel function of DHHC-containing palmitoyl acyltransferases (PATs) in mediating endothelial inflammation. Pharmacological inhibition of PATs attenuates barrier leakage and leucocyte adhesion induced by endothelial junction hyperpermeability and ICAM-1 expression during inflammation. Among 11 DHHCs detected in vascular endothelium, DHHC21 is required for barrier response. Mice with DHHC21 function deficiency (Zdhhc21dep/dep) exhibit marked resistance to injury, characterized by reduced plasma leakage, decreased leucocyte adhesion and ameliorated lung pathology, culminating in improved survival. Endothelial cells from Zdhhc21dep/dep display blunted barrier dysfunction and leucocyte adhesion, whereas leucocytes from these mice did not show altered adhesiveness. Furthermore, inflammation enhances PLCb1 palmitoylation and signalling activity, effects significantly reduced in Zdhhc21dep/dep and rescued by DHHC21 overexpression. Likewise, overexpression of wild-type, not mutant, PLCb1 augments barrier dysfunction. Altogether, these data suggest the involvement of DHHC21-mediated PLCb1 palmitoylation in endothelial inflammation.

Comments

For complete list of authors, please see article.

Copyright Statement

This document was originally published in Nature Communications by the Nature Publishing Group. This work is provided under a Creative Commons Attribution 4.0 license. Details regarding the use of this work can be found at: http://creativecommons.org/licenses/by/4.0/. doi: 10.1038/ncomms12823

Download

Share

COinS