Monochloramine inhibits the expression of E-selectin and intercellular adhesion molecule-1 induced by TNF-alpha through the suppression of NF-kappaB activation in human endothelial cells.

Reactive oxygen species have various effects on the expression of cell adhesion molecules induced by proinflammatory cytokines, such as tumor necrosis factor a (T-NF-alpha). We studied the effects of monochloramine (NH2Cl), a physiological oxidant derived from activated neutrophils, on the TNF-alpha-induced expression of E-selectin and intercellular adhesion molecule-1 (ICAM-1) in human umbilical vein endothelial cells (HUVEC). HUVEC were pretreated with or without NH2Cl (20-90 microM for 20 min), then stimulated with TNF-alpha (10 ng/ml), and the expression of E-selectin and ICAM-1 was measured. Without NH2Cl, TNF-alpha induced marked expression of e-selectin and ICAM-1. Pretreatment with NH2Cl resulted in a significant, but transient inhibition of the expression of adhesion molecules. Higher dose of NH2Cl showed more pronounced inhibition, and the inhibitory effect lasted for 8h when 70 microM of NH2Cl was added. TNF-alpha stimulation also induced marked activation of nuclear factor KB (NF-kappaB). Notably, NH2Cl also inhibited this NF-kappaB activation in a dose- and time-dependent manner, which was similar to the inhibition of E-selectin and ICAM-1 expression. In addition, IkappaB-alpha phosphorylation and degradation were also inhibited by NH2Cl pretreatment. These observations indicated that NH2Cl inhibited TNF-alpha-induced expression of E-selectin and ICAM-1 through the inhibition of NF-kappaB activation. We speculate that neutrophil-derived chloramines may have a regulatory role in the recruitment of leukocytes.