Cysteinyl leukotriene receptor type 1 (CysLT1R) antagonist zafirlukast protects against TNF-α-induced endothelial inflammation

In this study, we found that zafirlukast possesses beneficial protective effects on endothelial cells from TNF-α-induced inflammatory response and injury. Our results indicate that TNF-α treatment induces CysLT1R expression. The addition of zafirlukast to culture media suppressed TNF-α-induced expression of endothelial vascular adhesion molecules, such as ICAM-1, VCAM-1, and induction of cytokines, including IL-1β, IL-6, and IL-8. Zafirlukast also ameliorated production of reactive oxygen species (ROS) and adhesion of monocytes to endothelial cells induced by TNF-α. Mechanistically, we demonstrate that zafirlukast suppresses MAPK kinase p38 and NF-κB activation to inhibit inflammatory mediators. Collectively, our findings provide insights into the mechanisms of a potential therapeutic strategy for endothelial dysfunction-related diseases and shed light on the possible application of zafirlukast in cardiovascular diseases such as atherosclerosis.
Source: Biomedicine and Pharmacotherapy - Category: Drugs & Pharmacology Source Type: research