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rdf:type |
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lifeskim:mentions |
umls-concept:C0001128,
umls-concept:C0010467,
umls-concept:C0014597,
umls-concept:C0017262,
umls-concept:C0021760,
umls-concept:C0033634,
umls-concept:C0035820,
umls-concept:C0079633,
umls-concept:C0079904,
umls-concept:C0086418,
umls-concept:C0185117,
umls-concept:C0752312,
umls-concept:C1280500,
umls-concept:C1370600,
umls-concept:C1522619,
umls-concept:C2911684
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pubmed:issue |
2
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pubmed:dateCreated |
2009-1-27
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pubmed:abstractText |
Human esophageal epithelial cells play a key role in esophageal inflammation in response to acidic pH during gastroesophageal reflux disease (GERD), increasing secretion of IL-6 and IL-8. The mechanisms underlying IL-6 and IL-8 expression and secretion in esophageal epithelial cells after acid stimulation are not well characterized. We investigated the role of PKC, MAPK, and NF-kappaB signaling pathways and transcriptional regulation of IL-6 and IL-8 expression in HET-1A cells exposed to acid. Exposure of HET-1A cells to pH 4.5 induced NF-kappaB activity and enhanced IL-6 and IL-8 secretion and mRNA and protein expression. Acid stimulation of HET-1A cells also resulted in activation of MAPKs and PKC (alpha and epsilon). Curcumin, as well as inhibitors of NF-kappaB (SN-50), PKC (chelerythrine), and p44/42 MAPK (PD-098059) abolished the acid-induced expression of IL-6 and IL-8. The JNK inhibitor SP-600125 blocked expression/secretion of IL-6 but only partially attenuated IL-8 expression. The p38 MAPK inhibitor SB-203580 did not inhibit IL-6 expression but exerted a stronger inhibitory effect on IL-8 expression. Together, these data demonstrate that 1) acid is a potent inducer of IL-6 and IL-8 production in HET-1A cells; 2) MAPK and PKC signaling play a key regulatory role in acid-mediated IL-6 and IL-8 expression via NF-kappaB activation; and 3) the anti-inflammatory plant compound curcumin inhibits esophageal activation in response to acid. Thus IL-6 and IL-8 expression by acid may contribute to the pathobiology of mucosal injury in GERD, and inhibition of the NF-kappaB/proinflammatory cytokine pathways may emerge as important therapeutic targets for treatment of esophageal inflammation.
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Anthracenes,
http://linkedlifedata.com/resource/pubmed/chemical/Anti-Inflammatory Agents,
http://linkedlifedata.com/resource/pubmed/chemical/Benzophenanthridines,
http://linkedlifedata.com/resource/pubmed/chemical/Curcumin,
http://linkedlifedata.com/resource/pubmed/chemical/Flavonoids,
http://linkedlifedata.com/resource/pubmed/chemical/IL6 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/IL8 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Imidazoles,
http://linkedlifedata.com/resource/pubmed/chemical/Interleukin-6,
http://linkedlifedata.com/resource/pubmed/chemical/Interleukin-8,
http://linkedlifedata.com/resource/pubmed/chemical/Mitogen-Activated Protein Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/NF-kappa B,
http://linkedlifedata.com/resource/pubmed/chemical/PD 98059,
http://linkedlifedata.com/resource/pubmed/chemical/Peptides,
http://linkedlifedata.com/resource/pubmed/chemical/Protein Kinase C,
http://linkedlifedata.com/resource/pubmed/chemical/Protein Kinase Inhibitors,
http://linkedlifedata.com/resource/pubmed/chemical/Pyridines,
http://linkedlifedata.com/resource/pubmed/chemical/SB 203580,
http://linkedlifedata.com/resource/pubmed/chemical/SN50 peptide,
http://linkedlifedata.com/resource/pubmed/chemical/TERT protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Telomerase,
http://linkedlifedata.com/resource/pubmed/chemical/anthra(1,9-cd)pyrazol-6(2H)-one,
http://linkedlifedata.com/resource/pubmed/chemical/chelerythrine
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pubmed:status |
MEDLINE
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pubmed:month |
Feb
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pubmed:issn |
0193-1857
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:volume |
296
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
G388-98
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pubmed:dateRevised |
2009-11-19
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pubmed:meshHeading |
pubmed-meshheading:19074641-Anthracenes,
pubmed-meshheading:19074641-Anti-Inflammatory Agents,
pubmed-meshheading:19074641-Benzophenanthridines,
pubmed-meshheading:19074641-Cell Line,
pubmed-meshheading:19074641-Curcumin,
pubmed-meshheading:19074641-Enzyme Activation,
pubmed-meshheading:19074641-Epithelial Cells,
pubmed-meshheading:19074641-Esophagus,
pubmed-meshheading:19074641-Flavonoids,
pubmed-meshheading:19074641-Humans,
pubmed-meshheading:19074641-Hydrogen-Ion Concentration,
pubmed-meshheading:19074641-Imidazoles,
pubmed-meshheading:19074641-Interleukin-6,
pubmed-meshheading:19074641-Interleukin-8,
pubmed-meshheading:19074641-Mitogen-Activated Protein Kinases,
pubmed-meshheading:19074641-Mucous Membrane,
pubmed-meshheading:19074641-NF-kappa B,
pubmed-meshheading:19074641-Peptides,
pubmed-meshheading:19074641-Protein Kinase C,
pubmed-meshheading:19074641-Protein Kinase Inhibitors,
pubmed-meshheading:19074641-Pyridines,
pubmed-meshheading:19074641-Signal Transduction,
pubmed-meshheading:19074641-Telomerase,
pubmed-meshheading:19074641-Time Factors,
pubmed-meshheading:19074641-Transcription, Genetic,
pubmed-meshheading:19074641-Up-Regulation
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pubmed:year |
2009
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pubmed:articleTitle |
Effect of curcumin on acidic pH-induced expression of IL-6 and IL-8 in human esophageal epithelial cells (HET-1A): role of PKC, MAPKs, and NF-kappaB.
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pubmed:affiliation |
Department of Surgery, Medical College of Wisconsin, Milwaukee, WI 53226, USA. prafiee@mcw.edu
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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