RRC ID 1025
著者 Mori N, Krensky AM, Geleziunas R, Wada A, Hirayama T, Sasakawa C, Yamamoto N.
タイトル Helicobacter pylori induces RANTES through activation of NF-kappa B.
ジャーナル Infect Immun
Abstract Helicobacter pylori-infected gastric mucosa displays a conspicuous infiltration of mononuclear cells and neutrophils. RANTES (short for "regulated upon activation, normal T cell expressed and secreted") is a chemoattractant cytokine (chemokine) important in the infiltration of T lymphocytes and monocytes. RANTES may therefore contribute to the cellular infiltrate in the H. pylori-infected gastric mucosa. The aim of this study was to analyze the molecular mechanism responsible for H. pylori-mediated RANTES expression. We observed that gastric epithelial cells produced RANTES upon coculture with H. pylori. In addition, H. pylori induced RANTES mRNA expression and an increase in luciferase activity in cells which were transfected with a luciferase reporter construct derived from the RANTES promoter, in gastric epithelial cells, indicating that the induction of RANTES production occurred at the transcriptional level. Induction of RANTES was dependent on an intact cag pathogenicity island. Activation of the RANTES promoter by H. pylori occurred through the action of NF-kappa B. Transfection of kinase-deficient mutants of I kappa B kinase (IKK) and NF-kappa B-inducing kinase (NIK) inhibited H. pylori-mediated RANTES activation. In contrast, tumor necrosis factor alpha- or interleukin-1/Toll-like receptor signaling molecules-such as mitogen-activated protein kinase/extracellular signal-regulated kinase kinase 1, MyD88, and interleukin-1 receptor-associated kinase-did not play a role in RANTES activation by H. pylori. Collectively, H. pylori induced NF-kappa B activation through an intracellular signaling pathway that involved IKK and NIK, leading to RANTES gene transcription. RANTES induction by H. pylori may play an important role in gastric inflammation.
巻・号 71(7)
ページ 3748-56
公開日 2003-7-1
DOI 10.1128/IAI.71.7.3748-3756.2003
PMID 12819056
PMC PMC162018
MeSH Antineoplastic Agents / pharmacology Chemokine CCL5 / biosynthesis* Chemokine CCL5 / genetics Gastric Mucosa / metabolism Gastric Mucosa / microbiology Helicobacter pylori / pathogenicity* Humans Interleukin-1 / pharmacology Lipopolysaccharide Receptors / physiology Membrane Glycoproteins / physiology NF-kappa B / physiology* Nitriles* Organic Chemicals* Promoter Regions, Genetic RNA, Messenger / analysis Receptors, Cell Surface / physiology Sulfones* Toll-Like Receptors Transcription, Genetic
IF 3.201
引用数 22
WOS 分野 IMMUNOLOGY INFECTIOUS DISEASES
リソース情報
病原微生物