Next Article in Journal
Dorsal Root Injury—A Model for Exploring Pathophysiology and Therapeutic Strategies in Spinal Cord Injury
Next Article in Special Issue
Endothelial Dysfunction through Oxidatively Generated Epigenetic Mark in Respiratory Viral Infections
Previous Article in Journal
Perilipin 5 Ameliorates Hepatic Stellate Cell Activation via SMAD2/3 and SNAIL Signaling Pathways and Suppresses STAT3 Activation
Previous Article in Special Issue
Group V Phospholipase A2 Mediates Endothelial Dysfunction and Acute Lung Injury Caused by Methicillin-Resistant Staphylococcus Aureus
 
 
Article

Haloperidol Attenuates Lung Endothelial Cell Permeability In Vitro and In Vivo

1
Department of Medicine, Division of Pulmonary, Critical Care, Sleep and Allergy, University of Illinois Chicago, Chicago, IL 60607, USA
2
Room 920N (MC719), 840 S. Wood St., Chicago, IL 60612, USA
*
Author to whom correspondence should be addressed.
Academic Editor: Konstantin G. Birukov
Cells 2021, 10(9), 2186; https://doi.org/10.3390/cells10092186
Received: 19 May 2021 / Revised: 18 July 2021 / Accepted: 24 July 2021 / Published: 25 August 2021
(This article belongs to the Collection The Endothelial Cell in Lung Inflammation)
We previously reported that claudin-5, a tight junctional protein, mediates lung vascular permeability in a murine model of acute lung injury (ALI) induced by lipopolysaccharide (LPS). Recently, it has been reported that haloperidol, an antipsychotic medication, dose-dependently increases expression of claudin-5 in vitro and in vivo, in brain endothelium. Notably, claudin-5 is highly expressed in both brain and lung tissues. However, the effects of haloperidol on EC barrier function are unknown. We hypothesized that haloperidol increases lung EC claudin-5 expression and attenuates agonist-induced lung EC barrier disruption. Human pulmonary artery ECs were pretreated with haloperidol at variable concentrations (0.1–10 μM) for 24 h. Cell lysates were subjected to Western blotting for claudin-5, in addition to occludin and zona occludens-1 (ZO-1), two other tight junctional proteins. To assess effects on barrier function, EC monolayers were pretreated for 24 h with haloperidol (10 µM) or vehicle prior to treatment with thrombin (1 U/mL), with measurements of transendothelial electrical resistance (TER) recorded as a real-time assessment of barrier integrity. In separate experiments, EC monolayers grown in Transwell inserts were pretreated with haloperidol (10 µM) prior to stimulation with thrombin (1 U/mL, 1 h) and measurement of FITC-dextran flux. Haloperidol significantly increased claudin-5, occludin, and ZO-1 expression levels. Measurements of TER and FITC-dextran Transwell flux confirmed a significant attenuation of thrombin-induced barrier disruption associated with haloperidol treatment. Finally, mice pretreated with haloperidol (4 mg/kg, IP) prior to the intratracheal administration of LPS (1.25 mg/kg, 16 h) had increased lung claudin-5 expression with decreased lung injury as assessed by bronchoalveolar lavage (BAL) fluid protein content, total cell counts, and inflammatory cytokines, in addition to lung histology. Our data confirm that haloperidol results in increased claudin-5 expression levels and demonstrates lung vascular-protective effects both in vitro and in vivo in a murine ALI model. These findings suggest that haloperidol may represent a novel therapy for the prevention or treatment of ALI and warrants further investigation in this context. View Full-Text
Keywords: haloperidol; claudin-5; endothelial cells; vascular permeability; acute lung injury haloperidol; claudin-5; endothelial cells; vascular permeability; acute lung injury
Show Figures

Figure 1

MDPI and ACS Style

Colamonici, M.A.; Epshtein, Y.; Chen, W.; Jacobson, J.R. Haloperidol Attenuates Lung Endothelial Cell Permeability In Vitro and In Vivo. Cells 2021, 10, 2186. https://doi.org/10.3390/cells10092186

AMA Style

Colamonici MA, Epshtein Y, Chen W, Jacobson JR. Haloperidol Attenuates Lung Endothelial Cell Permeability In Vitro and In Vivo. Cells. 2021; 10(9):2186. https://doi.org/10.3390/cells10092186

Chicago/Turabian Style

Colamonici, Marco A., Yulia Epshtein, Weiguo Chen, and Jeffrey R. Jacobson. 2021. "Haloperidol Attenuates Lung Endothelial Cell Permeability In Vitro and In Vivo" Cells 10, no. 9: 2186. https://doi.org/10.3390/cells10092186

Find Other Styles
Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Article Access Map by Country/Region

1
Back to TopTop