Lipopolysaccharide activates nuclear factor kappaB in rat intestine: role of endogenous platelet-activating factor and tumour necrosis factor
Autor: | I G, De Plaen, X D, Tan, H, Chang, L, Wang, D G, Remick, W, Hsueh |
---|---|
Rok vydání: | 2000 |
Předmět: |
Cell Nucleus
Electrophoresis Lipopolysaccharides Male Neutrophils Tumor Necrosis Factor-alpha NF-kappa B Epithelial Cells Azepines Triazoles Immunohistochemistry Rats Intestines Rats Sprague-Dawley Ileum Papers Animals lipids (amino acids peptides and proteins) Intestinal Mucosa Platelet Activating Factor Antibodies Blocking Platelet Aggregation Inhibitors |
Zdroj: | British journal of pharmacology. 129(2) |
ISSN: | 0007-1188 |
Popis: | 1. We examined the effect of lipopolysaccharide (LPS), a cell wall constituent of Gram negative bacteria, on nuclear factor kappaB (NF-kappaB) 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-kappaB activation in response to PAF and LPS. 2. Ileal nuclear extracts from LPS (8 mg kg(-1), IV)-injected rats were assayed for NF-kappaB-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-kappaB p65 was localized by immunohistochemistry. An additional group was challenged with PAF (2 microg kg(-1), IV) for comparison. 3. LPS activates intestinal NF-kappaB, 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-kappaB 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 (P0.05). 4. LPS activates intestinal NF-kappaB in vivo and neutrophil activation is involved in its action. The LPS effect is mediated by both endogenous PAF and TNF. |
Databáze: | OpenAIRE |
Externí odkaz: |