Weibiao Cao

..In ulcerative colitis patients, spontaneous phasic contractions are decreased, and this decrease may be in part due to overproduction of hydrogen peroxide affecting sigmoid circular muscle...

..We conclude that H(2)O(2) may contribute to reduction of NKA-induced Ca(2+) release from intracellular Ca(2+) stores in UC and contribute to the observed colonic motor dysfunction...

..Sodium nitroprusside inhibited NKA but not the caffeine-induced Ca2+ signal. We conclude that in UC the mucosa releases IL-1beta, H2O2, and NO, which may contribute to the impaired Ca2+ release and altered sigmoid muscle contractility...

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..COX2-derived PGE2 production may contribute to NOX5-S-mediated cell proliferation in SEG1 cells...

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..Thus epithelial cells produce PAF in response to TRPV1-mediated calcium elevation...

..IL-1beta reproduces these changes, possibly by production of H(2)O(2) via sequential activation of MAPKs (ERK1/ERK2) and cPLA(2)...

..We conclude that Rac1 may be important in activation of NOX5-S in FLO EA cells...

..We conclude that H(2)O(2) may be at least partly responsible for impairment of Ca(2+) release in acute experimental esophagitis by inhibiting Ca(2+) uptake and refilling Ca(2+) stores...

..We conclude that a low dose of H(2)O(2) increases cell proliferation. H(2)O(2)-induced increase in cell proliferation may depend on sequential activation of ERK2 MAPK, NF-κB1 p50, and NOX5-S...

..H(2)O(2) causes formation of IL-1beta that may induce production of PAF in the muscle, possibly closing a self-sustaining cycle of production of inflammatory mediators...

..Bile acids may have an important role in this progression. This study aimed at examining the role of NADPH oxidase NOX5-S and a novel bile acid receptor TGR5 in taurodeoxycholic acid (TDCA)-induced increase in cell proliferation...

..IL-1beta appears to remain in the mucosa. In contrast, IL-6 is produced and released by the mucosa, eventually resulting in the production of H2O2 by the circular muscle, with this affecting circular muscle contraction...

..IL-6 causes production of H2O2, PAF, and other unidentified inflammatory mediators...

..The data support the validity of HET-1A cells as a model of the response of the human esophageal mucosa in GERD...

..Both H(2)O(2) and PGE(2) production depend on sequential activation of p38 MAPK and cPLA(2). cPLA(2) activates NADPH oxidases, producing H(2)O(2), and may produce arachidonic acid, converted to PGE(2) via COX-2...

..We conclude that HCl-induced activation of TRPV1 receptors in esophageal mucosa causes release of substance P and CGRP from neurons and release of PAF from epithelial cells...

..CONCLUSION: In patients with UC, IL-1 beta was increased in colonic circular muscles and may contribute to motor dysfunction after UC through production of hydrogen peroxide...

..Now, for the first time, we have obtained a human LES specimen with esophagitis (E-LES) and characterized its pathophysiologic mechanical and inflammatory profiles...

..The data suggest that the proinflammatory cytokines IL-1beta and IL-6 contribute to reduced esophageal contraction by inhibiting release of ACh from myenteric neurons...

..The data suggest that, in esophagitis, IL-1beta causes production of H(2)O(2). H(2)O(2) increases PGE(2), which relaxes the LES, and 8-iso-F(2alpha), which blocks PGF(2alpha)-mediated contraction...

..These data suggest that PKC-dependent contraction in ESO and LES is mediated by the following two distinct MAPK pathways: ERK1/2 and HSP27-linked p38 MAPK...

..This effect does not appear to be specific to PG because other steroid hormones such as aldosterone and testosterone can also induce it...

..Bile acids increase cell proliferation via activation of TGR5 receptors and G(q)α and Gα(i-3) proteins...

..This shift in signal-transduction pathways between initial and sustained contraction has been recently reported in intestinal smooth muscle...

..Acid-induced mPGES1 expression depends on activation of NOX5-S and NF-κB1 p50. Microsomal PGES1 may be a potential target to prevent or treat EA...

..Acid-induced NOX5-S expression depends on an increase in intracellular Ca(2+) and activation of CREB. NOX5-S contributes to increased cell proliferation and decreased apoptosis...

..At low concentrations, PGF(2alpha) activates PKC. At high concentration, it activates both a PKC- and a calmodulin-dependent pathway...

..We conclude that phosphatase inhibition potentiates the effects of MLCK in LES but not in ESO. Contraction of ESO is mediated by activation of PKCepsilon, MEK, ERK1/2, and ILK...

..4. Determine signaling pathways involved in the upregulation of COX-2 following acid exposure. 5. Determine whether IL-lb induces production of IL-6. ..

..Examining the relationship between inflammatory mechanisms and changes in motor function may help in understanding the functional disturbances associated with ulcerative colitis and identifying new targets for therapeutic intervention. ..

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..This project is designed to find potential therapeutic targets to prevent this progression. ..