Monochloramine Inhibits the Expression of E-selectin and Intercellular Adhesion Molecule-1 Induced by TNF-? Through the Suppression of NF-?B Activation in Human Endothelial Cells

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Abstract
Reactive oxygen species have various effects on the expression of cell adhesion molecules induced by pro-inflammatory cytokines, such as tumor necrosis factor f (TNF- f ). We studied the effects of monochloramine (NH 2 Cl), a physiological oxidant derived from activated neutrophils, on the TNF- f -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 NH 2 Cl (20-90 w M for 20 min), then stimulated with TNF- f (10 ng/ml), and the expression of e-selectin and ICAM-1 was measured. Without NH 2 Cl, TNF- f induced marked expression of e-selectin and ICAM-1. Pretreatment with NH 2 Cl resulted in a significant, but transient inhibition of the expression of adhesion molecules. Higher dose of NH 2 Cl showed more pronounced inhibition, and the inhibitory effect lasted for 8 h when 70 w M of NH 2 Cl was added. TNF- f stimulation also induced marked activation of nuclear factor s B (NF- s B). Notably, NH 2 Cl also inhibited this NF- s B activation in a dose- and time-dependent manner, which was similar to the inhibition of e-selectin and ICAM-1 expression. In addition, I s B- f phosphorylation and degradation were also inhibited by NH 2 Cl pretreatment. These observations indicated that NH 2 Cl inhibited TNF- f -induced expression of e-selectin and ICAM-1 through the inhibition of NF- s B activation. We speculate that neutrophil-derived chloramines may have a regulatory role in the recruitment of leukocytes.

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