TNF-α induced endothelial MAdCAM-1 expression is regulated by exogenous, not endogenous nitric oxide

نویسندگان

  • Tadayuki Oshima
  • Paul Jordan
  • Matthew B Grisham
  • Jonathan S Alexander
  • Merilyn Jennings
  • Makotoh Sasaki
  • Kenneth Manas
چکیده

BACKGROUND 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. METHODS 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. RESULTS AND DISCUSSION 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. CONCLUSIONS 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.

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عنوان ژورنال:
  • BMC Gastroenterology

دوره 1  شماره 

صفحات  -

تاریخ انتشار 2001