title: Effect of pertussis toxin and herbimycin A on proteinase-activated receptor 2-mediated cyclooxygenase 2 expression in Helicobacter pylori-infected gastric epithelial AGS cells.
abstract: Helicobacter pylori (H. pylori) is an important risk factor for chronic gastritis, peptic ulcer, and gastric cancer. Proteinase-activated receptor 2 (PAR2), subgroup of G-protein coupled receptor family, is highly expressed in gastric cancer, and chronic expression of cyclooxygenase-2 (COX-2) plays an important role in H. pylori-associated gastric carcinogenesis and inflammation. We previously demonstrated that H. pylori induced the expression of PAR2 and COX-2 in gastric epithelial cells. Present study aims to investigate whether COX-2 expression induced by H. pylori in Korean isolates is mediated by PAR2 via activation of G(i) protein and Src kinase in gastric epithelial AGS cells. Results showed that H. pylori-induced COX-2 expression was inhibited in the cells transfected with antisense oligonucleotide for PAR2 or treated with Gi protein blocker pertussis toxin, Src kinase inhibitor herbimycin A and soybean trypsin inbitor, indicating that COX-2 expression is mediated by PAR2 through activation of Gi protein and Src kinase in gastric epithelial cells infected with H. pylori in Korean isolates. Thus, targeting the activation of PAR2 may be beneficial for prevention or treatment of gastric inflammation and carcinogenesis associated with H. pylori infection.
authors.affiliation: Department Pharmacology, Brain Korea 21 Project for Medical Science, Yonsei University College of Medicine, Seoul, Korea. kim626@yonsei.ac.kr
authors.forename: Ji Hye
authors.initials: JH
authors.lastname: Seo
authors.forename: Jeong Yeon
authors.initials: JY
authors.lastname: Seo
authors.forename: Hae-Yun
authors.initials: HY
authors.lastname: Chung
authors.forename: Hyeyoung
authors.initials: H
authors.lastname: Kim
mesh_terms: D016227:Benzoquinones / Q000494:pharmacology*; D045744:Cell Line, Tumor; D051546:Cyclooxygenase 2 / Q000235:genetics / Q000378:metabolism*; D004847:Epithelial Cells / Q000201:enzymology / Q000378:metabolism / Q000382:microbiology; D019206:GTP-Binding Protein alpha Subunits, Gi-Go / Q000378:metabolism; D005753:Gastric Mucosa / Q000201:enzymology / Q000378:metabolism / Q000382:microbiology*; D016480:Helicobacter pylori; D006801:Humans; D047029:Lactams, Macrocyclic / Q000494:pharmacology*; D016376:Oligonucleotides, Antisense; D037342:Pertussis Toxin / Q000494:pharmacology*; D012333:RNA, Messenger / Q000378:metabolism; D044464:Receptor, PAR-2 / Q000502:physiology*; D017828:Rifabutin / Q000031:analogs & derivatives; D019061:src-Family Kinases / Q000378:metabolism
chemical_list: D016227:Benzoquinones; D047029:Lactams, Macrocyclic; D016376:Oligonucleotides, Antisense; D012333:RNA, Messenger; D044464:Receptor, PAR-2; D017828:Rifabutin; C020754:herbimycin; D051546:Cyclooxygenase 2; D037342:Pertussis Toxin; D019061:src-Family Kinases; D019206:GTP-Binding Protein alpha Subunits, Gi-Go