AIM: To investigate whether, or how, DA-9601, which is a new gastroprotective agent, inhibits TNF-α-induced inflammatory signals in gastric epithelial AGS cells. METHODS: Cell viability was determined by MTT assay. I...AIM: To investigate whether, or how, DA-9601, which is a new gastroprotective agent, inhibits TNF-α-induced inflammatory signals in gastric epithelial AGS cells. METHODS: Cell viability was determined by MTT assay. IL-8 and CCL20 promoter activities were determined by a luciferease reporter gene assay. NF-κB-dependent transcriptional activity was determined by I-κBαdegradation, NF-κB p65 nuclear translocation and a luciferase activity assay. IL-8 and CCL20 gene expression and protein secretion were determined by RT-PCR and an enzymelinked immunosorbent assay (ELISA). Total and phos-phorylated forms of mitogen-activated protein kinases (MAPKs) were determined by Western blot. RESULTS: Treatment of AGS cells with DA-9601 reduced TNF-α-induced IL-8 and CCL20 promoter activities, as well as their gene expression and protein release. TNF-αalso induced NF-κB-dependent transcriptional activity in AGS cells. In contrast, in cells treated with DA-9601, TNF-α-induced NF-κB activity was significantly blocked. Although all three MAP kinase family members were phosphorylated in response to TNF-α, a selective inhibitor of p38 kinase SB203580 only could inhibit both NF-κB-dependent transcriptional activity and IL-8 and CCL20 production, suggesting a potential link between p38 kinase and NF-κB-dependent pathways in AGS cells. Interestingly, DA-9601 also selectively inhibited p38 kinase phosphorylation induced by TNF-α. CONCLUSION: DA-9601 blocked TNF-α-mediated inflammatory signals by potentially modulating the p38 kinase pathway and/or a signal leading to NF-κBdependent pathways in gastric epithelial cells.展开更多
AIM： To evaluate the effect of ranitidine on gastric mucosal changes and on GI bleeding in long distance runhers. METHODS： Twenty-four long distance runners （M： 16, F： 8, age： 18.2＋ 1.5 years） participated in ...AIM： To evaluate the effect of ranitidine on gastric mucosal changes and on GI bleeding in long distance runhers. METHODS： Twenty-four long distance runners （M： 16, F： 8, age： 18.2＋ 1.5 years） participated in this study. A symptom questionnaire, stool hemoccult test, and upper gastrointestinal （GI） endoscopy were performed on the subjects prior to the study. The subjects took oral ranitidine （150 mg, b.i.d.） for two weeks. The upper GI endoscopy and stool Hemoccult tests were repeated after the treatment. RESULTS： Twenty-two of the 24 runners had at least one upper G1 mucosal lesion before the medication. The Endoscopic improvements were seen in eleven of the 14 cases of erosive gastritis and four of the 5 cases of esophagitis. Six subjects were Heine occult positive prior to the study, but only one was positive after the medication. CONCLUSION： Gastric mucosal lesions and GI bleeding in long distance runners seem to be associated to acidrelated factors mediated by the high level of regular running. Ranitidine seems to be and effective prophylaxis to prevent gastric mucosal lesions and GI bleeding.展开更多
基金Supported by grants from the Korea Health 21 R&D Project, Ministry of Health and Welfare, No.01-PJ3-PG6-01GN09-003, and the Korea Food and Drug Administration, No. 05142-620
文摘AIM: To investigate whether, or how, DA-9601, which is a new gastroprotective agent, inhibits TNF-α-induced inflammatory signals in gastric epithelial AGS cells. METHODS: Cell viability was determined by MTT assay. IL-8 and CCL20 promoter activities were determined by a luciferease reporter gene assay. NF-κB-dependent transcriptional activity was determined by I-κBαdegradation, NF-κB p65 nuclear translocation and a luciferase activity assay. IL-8 and CCL20 gene expression and protein secretion were determined by RT-PCR and an enzymelinked immunosorbent assay (ELISA). Total and phos-phorylated forms of mitogen-activated protein kinases (MAPKs) were determined by Western blot. RESULTS: Treatment of AGS cells with DA-9601 reduced TNF-α-induced IL-8 and CCL20 promoter activities, as well as their gene expression and protein release. TNF-αalso induced NF-κB-dependent transcriptional activity in AGS cells. In contrast, in cells treated with DA-9601, TNF-α-induced NF-κB activity was significantly blocked. Although all three MAP kinase family members were phosphorylated in response to TNF-α, a selective inhibitor of p38 kinase SB203580 only could inhibit both NF-κB-dependent transcriptional activity and IL-8 and CCL20 production, suggesting a potential link between p38 kinase and NF-κB-dependent pathways in AGS cells. Interestingly, DA-9601 also selectively inhibited p38 kinase phosphorylation induced by TNF-α. CONCLUSION: DA-9601 blocked TNF-α-mediated inflammatory signals by potentially modulating the p38 kinase pathway and/or a signal leading to NF-κBdependent pathways in gastric epithelial cells.
基金Supported by the 2005 research fund of Wonkwang University
文摘AIM： To evaluate the effect of ranitidine on gastric mucosal changes and on GI bleeding in long distance runhers. METHODS： Twenty-four long distance runners （M： 16, F： 8, age： 18.2＋ 1.5 years） participated in this study. A symptom questionnaire, stool hemoccult test, and upper gastrointestinal （GI） endoscopy were performed on the subjects prior to the study. The subjects took oral ranitidine （150 mg, b.i.d.） for two weeks. The upper GI endoscopy and stool Hemoccult tests were repeated after the treatment. RESULTS： Twenty-two of the 24 runners had at least one upper G1 mucosal lesion before the medication. The Endoscopic improvements were seen in eleven of the 14 cases of erosive gastritis and four of the 5 cases of esophagitis. Six subjects were Heine occult positive prior to the study, but only one was positive after the medication. CONCLUSION： Gastric mucosal lesions and GI bleeding in long distance runners seem to be associated to acidrelated factors mediated by the high level of regular running. Ranitidine seems to be and effective prophylaxis to prevent gastric mucosal lesions and GI bleeding.
