English (United Kingdom)

https://curated-unify.zendy.io/wp-json/zendy-region/v1/featured_content/oa?rat=en

https://curated-unify.zendy.io/wp-json/zendy-region/v1/highlighted_journal/

Global: Zendy Plus annual

Presents the access of premium content as premium feature

Premium Content

Presents the keyphrase highlighting as premium feature

Keyphrase Highlighting

Presents the summarisation as premium feature

Summarisation

Insights

Presents the pdf analysis as premium feature

PDF Analysis

Presents the zaia usage as premium feature

ZAIA

Global: Zendy Tools annual

Global: Zendy Free Plan

Global: Zendy Tools monthly

Global: Zendy Plus monthly

Many cells upon injury mount extensive, compensatory responses that increase cell survival; however, the intracellular signals that regulate these responses are not completely understood. Heparin-binding epidermal growth factor-like growth factor (HB-EGF) has been implicated as a cytoprotective agent. We have previously demonstrated that pretreatment of human intestinal epithelial cells with HB-EGF significantly decreased cytokine-induced activation of inducible NO synthase mRNA expression and NO production and protected the cells from apoptosis and necrosis. However, the mechanisms by which HB-EGF exerts these effects are not known. Here we show that cytokine exposure (IL-1beta and IFN-gamma) induced NF-kappaB activation and IL-8 and NO production in DLD-1 cells. Transient expression of a dominant negative form of IkappaBalpha decreased NO production, suggesting that the cytokines stimulated NO production in part through activation of NF-kappaB. HB-EGF dramatically suppressed NF-kappaB activity and IL-8 release and decreased NO production in cells pretreated with HB-EGF. HB-EGF blocked NF-kappaB activation by inhibiting IkappaB kinase activation and IkappaB phosphorylation and degradation, thus interfering with NF-kappaB nuclear translocation, DNA-binding activity, and NF-kappaB-dependent transcriptional activity. The data demonstrate that HB-EGF decreases inflammatory cytokine and NO production by interfering with the NF-kappaB signaling pathway. Inhibition of NF-kappaB may represent one of the mechanisms by which HB-EGF exerts its potent anti-inflammatory and cytoprotective effects.

Inhibition of NF-κB Activation and Its Target Genes by Heparin-Binding Epidermal Growth Factor-Like Growth Factor