Protein kinase C activation by Helicobacter pylori in human gastric epithelial cells limits interleukin-8 production through suppression of extracellular signal-regulated kinase.
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.
Nozawa
Yoshihisa
Y
Pharmacobioregulation Research Laboratory, Taiho Pharmaceutical Co, Ltd, Saitama, Japan. y-nozawa@taiho.co.jp
Nishihara
Katsushi
K
Akizawa
Yushiro
Y
Orimoto
Naoki
N
Nakano
Motoko
M
Uji
Tatsuya
T
Ajioka
Hirofusa
H
Kanda
Atsuhiro
A
Matsuura
Naosuke
N
Kiniwa
Mamoru
M
D000818:Animals; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000235:genetics / Q000378:metabolism; D015815:Cell Adhesion Molecules / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism / Q000382:microbiology*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000037:antagonists & inhibitors* / Q000187:drug effects / Q000378:metabolism; D005753:Gastric Mucosa / Q000166:cytology / Q000378:metabolism / Q000382:microbiology*; D016480:Helicobacter pylori / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D051550:I-kappa B Kinase; D007211:Indoles / Q000378:metabolism / Q000494:pharmacology; D016209:Interleukin-8 / Q000037:antagonists & inhibitors* / Q000096:biosynthesis / Q000737:chemistry; D008301:Maleimides / Q000378:metabolism / Q000494:pharmacology; D008722:Methods; D009281:Naphthalenes / Q000494:pharmacology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism* / Q000494:pharmacology; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D015815:Cell Adhesion Molecules; D007211:Indoles; D016209:Interleukin-8; D008301:Maleimides; D009281:Naphthalenes; D017346:Protein Serine-Threonine Kinases; C496559:CHUK protein, human; D051550:I-kappa B Kinase; C496560:IKBKB protein, human; C496565:IKBKE protein, human; D011493:Protein Kinase C; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D048049:Extracellular Signal-Regulated MAP Kinases; C058819:calphostin C; C070515:bisindolylmaleimide I; D013755:Tetradecanoylphorbol Acetate