Lipopolysaccharide activates nuclear factor κB in rat intestine:: role of endogenous platelet-activating factor and tumour necrosis factor

1 We examined the effect of lipopolysaccharide (LPS), a cell wall constituent of Gram negative bacteria, on nuclear factor kappa B (NF-kappa B) activation in the intestine and the roles of endogenous platelet-activating factor (PAF), tumour necrosis factor-alpha (TNF) and neutrophils. We also compared the time course of NF-kappa B activation in response to PAF and LPS. 2 Ileal nuclear extracts from LPS (8 mg kg(-1); IV)-injected rats were assayed for NF-kappa B-DNA-binding activity and identification of the subunits. Some rats were pretreated with WEB2170 (a PAF receptor antagonist), anti-TNF antibody, or anti-neutrophil antiserum. NF-kappa B p65 was localized by immunohistochemistry. An additional group was challenged with PAF (2 mu g kg(-1), IV) for comparison. 3 LPS activates intestinal NF-kappa B, both as p50-p50 and p50-p65 dimers within 15 min, and the effect peaks at 2 h. The effect is slower and more sustained than that of PAF, which peaks at 30 min. Activated NF-kappa B was immunolocalized within epithelial and lamina propria cells. LPS effect was reduced by 41, 37 and 44%, respectively, in animals pretreated with WEB2170, anti-TNF antibody, or anti-neutrophil antiserum (P < 0.05). 4 LPS activates intestinal NF-kappa B in vivo and neutrophil activation is involved in its action. The LPS effect is mediated by both endogenous PAF and TNF.