2-2--(hydroxynitrosohydrazono)bis-ethanamine and Inflammatory-Bowel-Diseases

MAdCAM-1 is an adhesion molecule expressed in Peyer's patches and lymphoid tissues which is mobilized by cytokines like TNF-alpha and is a major determinant of lymphocyte trafficking to the gut in human inflammatory bowel disease (IBD). It has been suggested that both reactive oxygen and nitrogen metabolites participate in regulating adhesion molecule expression in response to TNF-alpha.. To examine how exogenous and endogenous sources of NO modulate MAdCAM-1 induction by TNF-alpha, we pre-treated mouse lymphatic endothelial cells with either long or short acting NO donors prior to TNF-alpha-stimulation, and measured MAdCAM-1 induction at 24 h.. DETA-NO, a long-acting NO donor, and SperNO, a rapid releasing NO donor both inhibited TNF-alpha-stimulated MAdCAM-1 expression in a concentration dependent manner. Both NO donors also reduced a4b7-dependent lymphocyte endothelial adhesion. Inhibition of endogenous NO production by either L-NAME, a non-selective NOS inhibitor, or by 1400 w, a selective iNOS inhibitor failed to induce, or potentiate TNF-alpha regulated MAdCAM-1 expression.. Exogenous NO donors may be beneficial in the treatment of IBD, while endogenous nitric oxide synthases may be less effective in controlling adhesion molecule expression in response to cytokines.

Topics: Amidines; Animals; Benzylamines; CD8-Positive T-Lymphocytes; Cell Adhesion; Cell Adhesion Molecules; Cell Line; Endothelium; Immunoblotting; Immunoglobulins; Inflammatory Bowel Diseases; Mice; Mucoproteins; Nitric Oxide; Nitric Oxide Donors; Nitric Oxide Synthase; Nitrogen Oxides; Reverse Transcriptase Polymerase Chain Reaction; Spermine; Triazenes; Tumor Necrosis Factor-alpha