Alleviation of LPS-induced Endothelial Injury due to GHRH Antagonist Treatment.
Saikat Fakir, Khadeja-Tul Kubra, Mohammad Shohel Akhter, Mohammad Afaz Uddin, Nektarios Barabutis
Author Information
Saikat Fakir: School of Basic Pharmaceutical and Toxicological Sciences, College of Pharmacy, University of Louisiana Monroe, 1800 Bienville Drive, Monroe, LA 71201, USA.
Khadeja-Tul Kubra: School of Basic Pharmaceutical and Toxicological Sciences, College of Pharmacy, University of Louisiana Monroe, 1800 Bienville Drive, Monroe, LA 71201, USA.
Mohammad Shohel Akhter: School of Basic Pharmaceutical and Toxicological Sciences, College of Pharmacy, University of Louisiana Monroe, 1800 Bienville Drive, Monroe, LA 71201, USA.
Mohammad Afaz Uddin: School of Basic Pharmaceutical and Toxicological Sciences, College of Pharmacy, University of Louisiana Monroe, 1800 Bienville Drive, Monroe, LA 71201, USA.
Nektarios Barabutis: School of Basic Pharmaceutical and Toxicological Sciences, College of Pharmacy, University of Louisiana Monroe, 1800 Bienville Drive, Monroe, LA 71201, USA.
Background: GHRH is produced in the hypothalamus and affects various tissues beyond the pituitary, including the lungs. GHRH antagonists exert anti-inflammatory properties in several experimental models of disease, but their role inprotecting the endothelial barrier during inflammation is less understood. This study investigates the effects ofGHRHAnt on LPS-induced endothelial dysfunction. Methods: BPAEC and HMVEC-L cells were exposed to LPS to induce endothelial injury. GHRHAnt was administered eitherpre- or post-LPS treatment. Western blot analysis was used to evaluate protein expression levels. Paracellularpermeability was assessed utilizing FITC-dextran assay to evaluate endothelial barrier function. Results: GHRHAnt post-treatment significantly reduced LPS-induced MLC2 phosphorylation and cofilin activation inBPAECs. Furthermore, pretreatment with GHRHAnt enhanced barrier function and ameliorated LPS-inducedhyperpermeability in both human and bovine endothelial cells. Conclusions: GHRHAnt treatment mitigates LPS-induced endothelial barrier dysfunction. These findings suggest that GHRHAntcould serve as potential therapeutic agents towards endothelial dysfunction-related illness (e.g. sepsis).
