Cha Boram, Kim Kyung Hwan, Kim Hyeyoung
Department of Pharmacology and Institute of Gastroenterology, Brain Korea 21 Project, Yonsei University College of Human Ecology, Seoul, Korea.
Ann N Y Acad Sci. 2009 Aug;1171:457-63. doi: 10.1111/j.1749-6632.2009.04706.x.
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.
幽门螺杆菌会破坏控制胃上皮细胞凋亡与细胞增殖之间稳态的基因。核因子-κB（NF-κB）在幽门螺杆菌诱导的胃上皮细胞凋亡中起重要作用。过氧化物酶体增殖物激活受体-γ配体15-脱氧-Δ（12,14）-前列腺素J2（15d-PGJ2）调节幽门螺杆菌感染的胃上皮细胞的生长和信号级联反应。在本研究中，我们确定15d-PGJ2是否通过调节感染CagA+、VacA+的韩国分离株（HP99）幽门螺杆菌的胃上皮细胞中的凋亡基因表达和NF-κB激活来抑制凋亡。发现15d-PGJ2可抑制幽门螺杆菌诱导的DNA片段化和细胞死亡。15d-PGJ2可诱导胃上皮细胞中促凋亡蛋白Bax的下调和抗凋亡蛋白Bcl-2的上调，以及抑制幽门螺杆菌引起的NF-κB激活。结果表明，15d-PGJ2通过抑制胃上皮细胞中的NF-κB激活和凋亡基因表达来抑制凋亡性细胞死亡。
