RRC ID 42119
Author Nozawa Y, Nishihara K, Akizawa Y, Orimoto N, Nakano M, Uji T, Ajioka H, Kanda A, Matsuura N, Kiniwa M.
Title Protein kinase C activation by Helicobacter pylori in human gastric epithelial cells limits interleukin-8 production through suppression of extracellular signal-regulated kinase.
Journal J Pharmacol Sci
Abstract Helicobacter pylori (H. pylori) infection of gastric epithelial cells has been shown to induce interleukin (IL)-8 production, but the signal transduction mechanism leading to IL-8 production has not been clearly defined. Here, we investigate the role of protein kinase C (PKC) in the mechanism of induction of IL-8 release by H. pylori in human gastric epithelial cells. In MKN45 cells, H. pylori-induced IL-8 release was enhanced by treatment with PKC inhibitors (GF109203X and calphostin C) and PKC depletion, which completely inhibited PKC activity. Moreover, PKC inhibitors and PKC depletion increased extracellular signal-regulated kinase (ERK) activity and phosphorylation, but not calcium/calmodulin-dependent protein kinase II (CaMK II) activity, in response to H. pylori infection. PKC activated by H. pylori inhibited activation of ERK induced by H. pylori without affecting the CaMK II activity and negatively regulated IL-8 production in human gastric epithelial cells.
Volume 94(3)
Pages 233-9
Published 2004-3-1
DOI 10.1254/jphs.94.233
PMID 15037807
MeSH Animals Calcium-Calmodulin-Dependent Protein Kinases / genetics Calcium-Calmodulin-Dependent Protein Kinases / metabolism Cell Adhesion Molecules / drug effects Cell Survival / drug effects Cell Survival / physiology Dose-Response Relationship, Drug Down-Regulation Epithelial Cells / drug effects Epithelial Cells / metabolism Epithelial Cells / microbiology* Extracellular Signal-Regulated MAP Kinases / antagonists & inhibitors* Extracellular Signal-Regulated MAP Kinases / drug effects Extracellular Signal-Regulated MAP Kinases / metabolism Gastric Mucosa / cytology Gastric Mucosa / metabolism Gastric Mucosa / microbiology* Helicobacter pylori / drug effects Helicobacter pylori / genetics Helicobacter pylori / metabolism* Humans I-kappa B Kinase Indoles / metabolism Indoles / pharmacology Interleukin-8 / antagonists & inhibitors* Interleukin-8 / biosynthesis Interleukin-8 / chemistry Maleimides / metabolism Maleimides / pharmacology Methods Naphthalenes / pharmacology Protein Kinase C / antagonists & inhibitors Protein Kinase C / metabolism* Protein Kinase C / pharmacology Protein-Serine-Threonine Kinases / metabolism Tetradecanoylphorbol Acetate / pharmacology Tumor Cells, Cultured
IF 2.835
Times Cited 9
WOS Category PHARMACOLOGY & PHARMACY
Resource
Human and Animal Cells