Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0042109 (urticaria)
 6,569 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Caffeic acid phenethyl ester (CAPE), an active component of propolis from honeybee hives, is known to have antimitogenic, anticarcinogenic, antiinflammatory, and immunomodulatory properties. The molecular basis for these diverse properties is not known. Since the role of the nuclear factor NF-kappa B in these responses has been documented, we examined the effect of CAPE on this transcription factor. Our results show that the activation of NF-kappa B by tumor necrosis factor (TNF) is completely blocked by CAPE in a dose- and time-dependent manner. Besides TNF, CAPE also inhibited NF-kappa B activation induced by other inflammatory agents including phorbol ester, ceramide, hydrogen peroxide, and okadaic acid. Since the reducing agents reversed the inhibitory effect of CAPE, it suggests the role of critical sulfhydryl groups in NF-kappa B activation. CAPE prevented the translocation of the p65 subunit of NF-kappa B to the nucleus and had no significant effect on TNF-induced I kappa B alpha degradation, but did delay I kappa B alpha resynthesis. The effect of CAPE on inhibition of NF-kappa B binding to the DNA was specific, in as much as binding of other transcription factors including AP-1, Oct-1, and TFIID to their DNA were not affected. When various synthetic structural analogues of CAPE were examined, it was found that a bicyclic, rotationally constrained, 5,6-dihydroxy form was superactive, whereas 6,7-dihydroxy variant was least active. Thus, overall our results demonstrate that CAPE is a potent and a specific inhibitor of NF-kappa B activation and this may provide the molecular basis for its multiple immunomodulatory and antiinflammatory activities.
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PMID:Caffeic acid phenethyl ester is a potent and specific inhibitor of activation of nuclear transcription factor NF-kappa B. 879 59

Caffeic acid phenethyl ester (CAPE), an active component of propolis from honeybee hives (honeybee resin), has anti-inflammatory, anti-carcinogenic and anti-bacterial properties. This study was designed to investigate the anti-inflammatory effects of CAPE on Helicobacter pylori-induced NF-kappaB and AP-1 in the gastric epithelial cell line AGS. Electrophoretic mobility shift assay was used to measure NF-kappaB- and AP-1-DNA binding activity. Western blotting was used to detect IkappaB-alpha and COX-2 expression in AGS cells cocultured with H. pylori. The antiproliferative effect of CAPE was measured by MTT assay. Our results showed that caffeic phenethyl ester inhibits H. pylori-induced NF-kappaB and AP-1 DNA-binding activity in a dose (0.1-25 microg ml(-1) approximately 0.35-88 microM) and time- (15-240 min) dependent manner in AGS cells. Maximum inhibition by CAPE was observed at concentrations of 25 microg ml(-1) ( approximately 88 microM) CAPE prevented H. pylori- and cytokine-induced degradation of IkappaB-alpha protein. Pretreatment of AGS cells with CAPE also blocked cytokine- and mitogen-induced NF-kappaB and AP-1 expression. Furthermore, CAPE suppressed H. pylori-induced cell proliferation and production of the cytokines TNF-alpha and IL-8. In addition, CAPE blocked H. pylori-induced COX-2 expression. The inhibition of such transcription by CAPE could result in suppression of many genes during H. pylori-induced inflammation, and also provide new insights into the anti-cancer and anti-inflammatory properties of CAPE.
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PMID:Caffeic acid phenethyl ester modulates Helicobacter pylori-induced nuclear factor-kappa B and activator protein-1 expression in gastric epithelial cells. 1624 12