Helicobacter pylori extract induces nuclear factor-kappa B, activator protein-1, and cyclooxygenase-2 in esophageal epithelial cells.
Helicobacter pylori infection is recognized as the major cause of gastritis and gastric cancer; however, its role in the development of gastroesophageal reflux disease and Barrett's adenocarcinoma is unclear. The expression of NF-kappaB, AP-1, and COX-2 may be important in inflammation and tumorigenesis in the esophagus. The aim of this study was to examine the effect of live H pylori or H pylori extract (HPE) on these factors in the esophageal epithelial cell lines SKGT-4 and OE33. NF-kappaB and AP-1 activity were assessed by gel shift assay and COX-2 by Western blotting. Coculture of SKGT-4 and OE33 with live H pylori and HPE induced NF-kappaB and AP-1 DNA-binding activity, and also decreased IkappaB-alpha levels. Treatment with the specific MEK1/2 MAPK inhibitor PD98059, but not the p38 MAPK inhibitor SB203580, inhibited NF-kappaB and AP-1 activity. The antioxidant vitamin C inhibited H pylori-induced NF-kappaB activation, but increased AP-1 expression. Moreover, HPE induced COX-2 expression and IL-8 production, and PD98059 inhibited COX-2 expression, ERK1/2 phosphorylation, and IL-8 production. These data demonstrate that both live H pylori and HPE induce NF-kappaB and AP-1 expression in esophageal epithelial cells. The induction of such transcription factors may play a role in the specific immune response within Barrett's mucosa and may indirectly cause inflammation of the gastric cardia and the distal esophagus.
Abdel-Latif
Mohamed M M
MM
Department of Surgery and Clinical Medicine, Trinity Centre for Health Sciences, St. James's Hospital, Dublin, Ireland. abdellmm@tcd.ie
Windle
Henry
H
Terres
Ana
A
Eidhin
Déirdre Ní
DN
Kelleher
Dermot
D
Reynolds
John V
JV
D000975:Antioxidants / Q000494:pharmacology; D001205:Ascorbic Acid / Q000494:pharmacology; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000037:antagonists & inhibitors; D002457:Cell Extracts; D045744:Cell Line, Tumor; D051546:Cyclooxygenase 2 / Q000096:biosynthesis* / Q000187:drug effects; D052246:Cyclooxygenase 2 Inhibitors / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism; D004947:Esophagus / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D005419:Flavonoids / Q000494:pharmacology; D016480:Helicobacter pylori / Q000378:metabolism*; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology; D016209:Interleukin-8 / Q000096:biosynthesis; D048369:MAP Kinase Kinase 1 / Q000037:antagonists & inhibitors; D019950:Mitogen-Activated Protein Kinase 1 / Q000187:drug effects; D048052:Mitogen-Activated Protein Kinase 3 / Q000187:drug effects; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000096:biosynthesis*; D010766:Phosphorylation / Q000187:drug effects; D011725:Pyridines / Q000494:pharmacology; D015398:Signal Transduction / Q000502:physiology; D018808:Transcription Factor AP-1 / Q000037:antagonists & inhibitors / Q000096:biosynthesis*
D000975:Antioxidants; D002457:Cell Extracts; D052246:Cyclooxygenase 2 Inhibitors; D004791:Enzyme Inhibitors; D005419:Flavonoids; D007093:Imidazoles; D016209:Interleukin-8; D016328:NF-kappa B; D011725:Pyridines; D018808:Transcription Factor AP-1; D051546:Cyclooxygenase 2; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases; D048369:MAP Kinase Kinase 1; C093642:SB 203580; D001205:Ascorbic Acid; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one