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This Article Full Text Full Text (PDF) All Versions of this Article: 296/2/G388    most recent 90428.2008v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Rafiee, P. Articles by Shaker, R. Search for Related Content PubMed PubMed Citation Articles by Rafiee, P. Articles by Shaker, R.

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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-B

Departments of ¹Surgery and ²Medicine, Medical College of Wisconsin, Milwaukee, Wisconsin; ³Department of Medicine B, University Hospital Muenster, Muenster, Germany; and ⁴Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania

Submitted 11 July 2008 ; accepted in final form 9 December 2008

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-B 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-B 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 ( and ). Curcumin, as well as inhibitors of NF-B (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-B 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-B/proinflammatory cytokine pathways may emerge as important therapeutic targets for treatment of esophageal inflammation.

gastroesophageal reflux disease; interleukin-6; interleukin-8

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