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• W1598082102 abstract "Bacterial endotoxin (lipopolysaccharide; LPS) and platelet-activating factor (PAF) are important triggers of bowel inflammation and injury. We have previously shown that LPS activates the transcription factor nuclear factor (NF)-κB in the intestine, which up-regulates many pro-inflammatory genes. This effect partly depends on neutrophils and endogenous PAF. However, whether LPS and PAF directly activate NF-κB in enterocytes remains controversial. In this study, we first investigated the effect of LPS and PAF on NF-κB activation in IEC-6 (a non-transformed rat small intestinal crypt cell line) cells, by electrophoresis mobility shift assay and supershift, and found that LPS, but not PAF, activates NF-κB mostly as p50–p65 heterodimers. The effect was slower than tumour necrosis factor (TNF). Both LPS and TNF induce the expression of the NF-κB-dependent gene inducible nitric oxide synthase (iNOS), which occurs subsequent to NF-κB activation. We then examined the effect of LPS and TNF on the inhibitory molecules IκBα and IκBβ. We found that TNF causes rapid degradation of IκBα and IκBβ. In contrast, LPS did not change the levels of IκBα and IκBβ up to 4 hr (by Western blot). However, in the presence of cycloheximide, there was a slow reduction of IκBα and IκBβ, which disappeared almost completely at 4 hr. These observations suggest that LPS causes slow degradation and synthesis of IκBα and IκBβ and therefore activates NF-κΒ via at least two mechanisms: initially, through an IκB-independent mechanism, and later, via an increased turnover of the inhibitor IκB. NF-κΒ activation precedes the gene expression of iNOS (assayed by reverse transcription–polymerase chain reaction), suggesting that LPS up-regulates iNOS via this transcription factor." @default.
• W1598082102 created "2016-06-24" @default.
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• W1598082102 date "2002-08-01" @default.
• W1598082102 modified "2023-10-12" @default.
• W1598082102 title "Endotoxin, but not platelet-activating factor, activates nuclear factor-kappaB and increases IkappaBalpha and IkappaBbeta turnover in enterocytes" @default.
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• W1598082102 doi "https://doi.org/10.1046/j.1365-2567.2002.01453.x" @default.
• W1598082102 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/1782741" @default.
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