Polymorphonuclear leukocyte (PMN) migration across vascular endothelial cells (EC) in the absence or presence of IL‐1β differentially regulate expression of EC adhesion molecules ICAM‐1 and E‐selectin

Abstract

Our findings indicate that PMN migration across activated EC results in down‐regulation of EC nuclear transcription factor, NFκB. However, the subsequent functional consequences are largely unknown.In this study we assessed the effects of PMN transendothelial migration on NFκB‐dependent expression of EC adhesion molecules, ICAM‐1 and E‐selectin during inflammation.To this end human endothelial cells (HUVEC) were grown in Traswell inserts and stimulated with IL‐1β (1ng/ml; 4 hrs). Subsequently, PMN were added and allowed to migrate across HUVEC in response to fMLP (10−8M) chemotactic gradient in the absence (i.e. across washed HUVEC) or presence of IL‐1β. ICAM‐1 and E‐selectin gene expression in EC was assessed by RT‐PCR after 4 or 24 hrs following PMN migration.The obtained results indicate that migration of PMN across IL‐1β treated and subsequently washed HUVEC results in a marked down‐regulation of IL‐1 β‐induced ICAM‐1, and to a lesser degree, E‐selectin gene expression as assessed 4 and 24 hrs following PMN migration. On the contrary, migration of PMN across activated HUVEC in the presence of IL‐1β results in a further increase in both, ICAM‐1 and E‐selectin expression.Taken together these findings indicate that migrating PMN differentially modulate expression of EC adhesion molecules during inflammation and can offer EC with both, anti‐ and pro‐inflammatory stimuli (HSFO‐NA5580/NA6171)