Fasudil inhibits neutrophil-endothelial cell interactions by regulating the expressions of GRP78 and BMPR2

Experimental Cell Research
Jingjing WangHui Kong

Abstract

Regulation of leukocyte-endothelial cell interactions and of vascular permeability plays a critical role in the maintenance of functional pulmonary microvascular barriers. Little is yet known about the effect of the Rho-associated protein kinase (ROCK) inhibitor fasudil on leukocyte-endothelial cell interactions or the underlying mechanism. In the present study, as evaluated using co-culture systems of neutrophils and human pulmonary microvascular endothelial cells (HPMECs), fasudil dose-dependently suppressed neutrophil chemotaxis by decreasing the production of chemotactic factors in lipopolysaccharide (LPS)-treated HPMECs. The inhibitory role of fasudil in neutrophil chemotaxis was mediated by down-regulation of the chaperone glucose-regulated protein 78 (GRP78), since the inhibition was abolished by 4-phenyl butyric acid (a chemical chaperone mimicking GRP78). In addition, fasudil inhibited LPS-induced neutrophil-endothelial adhesion by reducing the expression of intercellular adhesion molecule (ICAM)-1. By use of lentiviral transfection in HPMECs, bone morphogenic protein receptor 2 (BMPR2) overexpression suppressed the LPS-induced increase of both ICAM-1 expression and neutrophil-endothelial adhesion, whereas knocking dow...Continue Reading

Citations

May 24, 2018·Laboratory Investigation; a Journal of Technical Methods and Pathology·Jian XuHui Kong
Sep 30, 2020·Genes·Fay Newton, Roly Megaw
Apr 24, 2020·American Journal of Physiology. Lung Cellular and Molecular Physiology·Andrew J GoodwinHongkuan Fan
Apr 4, 2021·International Journal of Molecular Sciences·Asfia SoomroJoan C Krepinsky
Mar 5, 2019·Biochemical Pharmacology·Christian Bailly, Michael J Waring
May 15, 2021·Frontiers in Immunology·Isaac M RichardsonLaurel E Hind
Aug 28, 2021·Cells·Maria Luísa da Silveira Hahmeyer, José Eduardo da Silva-Santos
Nov 25, 2021·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Yanjiang XingJun Yang

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