Pharmacological consequence of inhibiting MAPK p38 using Ralimetinib dimesylate on lipopolysaccharide-induced E-selectin and VCAM-1 expression in HUVEC

• Main Author: Dayang Erna Zulaikha, Awang Hamsin
• Format: Proceeding
• Language: English
• Published: 2022
• Subjects: RM Therapeutics. Pharmacology
• Online Access: http://ir.unimas.my/id/eprint/45861/3/Pharmacological%20consequence.pdf; http://ir.unimas.my/id/eprint/45861/

Endothelial dysfunction plays a prominent role in the pathogenesis of sepsis and is associated with life-threatening organ dysfunction. Lipopolysaccharide (LPS), a Gram-negative bacterial component, is an important sepsis associated mediator that induces the expression of adhesion molecules such as E-selectin and VCAM-1 upon its binding to dedicated pattern recognition receptors on endothelial cells (EC) [1]. Endothelial E-selectin and VCAM-1 expression promotes leukocyte adhesion, and high leukocyte infiltration in various organs is associated with a poor prognosis in sepsis patients. As the expression of E-selectin and VCAM-1 is partly driven by the activation of the MAPK p38 signaling pathway [2], it is unknown whether Ralimetinib dimesylate (RM), a selective p38 MAPK inhibitor, can be used as a treatment to reduce E-selectin and VCAM-1 expression once LPS-driven activation of EC has started. RM treatment was previously shown to reduce TNF-α production in LPS-induced macrophages in vitro [3]. In this study, I investigated the pharmacological effect of RM treatment on E-selectin and VCAM-1 expression in LPS-stimulated HUVEC was investigated.