15-Deoxy-delta 12, 14,-prostaglandin J2 suppresses nuclear factor-kappaB-mediated apoptosis of Helicobacter pylori-infected gastric epithelial cells.
Helicobacter pylori deregulates the genes that control homeostasis between apoptosis and cell proliferation of gastric epithelial cells. Nuclear factor-kappaB (NF-kappaB) has an important role in H. pylori-induced apoptosis in gastric epithelial cells. The peroxisome proliferator-activated receptor-gamma ligand 15-deoxy-Delta(12,14)-prostaglandin J(2) (15d-PGJ(2)) regulates growth and the signaling cascade in H. pylori-infected gastric epithelial cells. In the present study, we determined whether 15d-PGJ(2) inhibits apoptosis by regulating apoptotic gene expression and NF-kappaB activation in gastric epithelial cells infected with CagA+, VacA+H. pylori in a Korean isolate (HP99). 15d-PGJ(2) was found to inhibit H. pylori-induced DNA fragmentation and cell death. 15d-PGJ(2) induced downregulation of proapoptotic Bax and upregulation of antiapoptotic Bcl-2 as well as suppression of NF-kappaB activation caused by H. pylori in gastric epithelial cells. The results suggest that 15d-PGJ(2) inhibits apoptotic cell death by inhibiting NF-kappaB activation and apoptotic gene expression in gastric epithelial cells.
Cha
Boram
B
Department of Pharmacology and Institute of Gastroenterology, Brain Korea 21 Project, Yonsei University College of Human Ecology, Seoul, Korea.
Kim
Kyung Hwan
KH
Kim
Hyeyoung
H
D000230:Adenocarcinoma / Q000378:metabolism / Q000382:microbiology / Q000473:pathology; D000942:Antigens, Bacterial / Q000235:genetics; D017209:Apoptosis / Q000187:drug effects*; D001426:Bacterial Proteins / Q000235:genetics; D015153:Blotting, Western; D045744:Cell Line, Tumor; D053938:DNA Fragmentation / Q000187:drug effects; D024202:Electrophoretic Mobility Shift Assay; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D016480:Helicobacter pylori / Q000235:genetics / Q000254:growth & development*; D006801:Humans; D016328:NF-kappa B / Q000378:metabolism*; D009841:Oligonucleotides / Q000235:genetics / Q000378:metabolism; D015230:Prostaglandin D2 / Q000031:analogs & derivatives / Q000494:pharmacology; D011485:Protein Binding / Q000187:drug effects; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D013274:Stomach Neoplasms / Q000378:metabolism / Q000382:microbiology / Q000473:pathology; D051028:bcl-2-Associated X Protein / Q000378:metabolism
C097240:15-deoxy-delta(12,14)-prostaglandin J2; D000942:Antigens, Bacterial; D001426:Bacterial Proteins; D016328:NF-kappa B; D009841:Oligonucleotides; D019253:Proto-Oncogene Proteins c-bcl-2; C074689:VacA protein, Helicobacter pylori; D051028:bcl-2-Associated X Protein; C080866:cagA protein, Helicobacter pylori; D015230:Prostaglandin D2