Nageen Sharma
Craniosacral therapy
Federal Hostels , Faisalabad, Punjab, Pakistan, 38000
Years of experience 3

Total years in practice: 3

Published Date
February 01, 2009
Abstract Authors
Parvaneh Rafiee, Victoria M Nelson, Sharon Manley, Michael Wellner, Martin Floer, David G Binion, Reza Shaker
Abstract Source
Am J Physiol Gastrointest Liver Physiol. 2009 Feb;296(2):G388-98. Epub 2008 Dec 12. PMID: 19074641
Study Type
Therapeutic Substances
Constipation, High Cholesterol
Holistic Medicine, Naturopathic Medicine
Abstract Content
Human esophageal epithelial cells play a key role in esophageal inflammation in response to acidic pH during gastroesophageal reflux (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.
Get a Consultation
(650) 539-4545
Get more information via email