RT Journal Article
SR Electronic
T1 Tumor Necrosis Factor-α-Induced Cytokine-Induced Neutrophil Chemoattractant-1 (CINC-1) Production by Rat Gastric Epithelial Cells: Role of Reactive Oxygen Species and Nuclear Factor-κB
JF Journal of Pharmacology and Experimental Therapeutics
JO J Pharmacol Exp Ther
FD American Society for Pharmacology and Experimental Therapeutics
SP 670
OP 676
DO 10.1124/jpet.103.062216
VO 309
IS 2
A1 Handa, Osamu
A1 Naito, Yuji
A1 Takagi, Tomohisa
A1 Shimozawa, Makoto
A1 Kokura, Satoshi
A1 Yoshida, Norimasa
A1 Matsui, Hirofumi
A1 Cepinskas, Gediminas
A1 Kvietys, Peter R.
A1 Yoshikawa, Toshikazu
YR 2004
UL http://jpet.aspetjournals.org/content/309/2/670.abstract
AB Rat cytokine-induced neutrophil chemoattractant-1 (CINC-1), a counterpart of the human growth-regulated oncogene product (GRO), has been suggested to participate in neutrophil recruitment in an experimental model of gastritis in rat. However, the mechanism(s) involved in regulation of CINC-1 production by the gastric mucosa remains unclear. The aim of this study was to investigate the mechanism(s) of CINC-1 production by rat gastric mucosa in vitro. All experiments were performed using rat normal gastric mucosal cell line (RGM-1). RGM-1s were stimulated with tumor necrosis factor (TNF)-α, and CINC-1 mRNA levels (reverse transcription-polymerase chain reaction) and protein secretion (enzyme-linked immunosorbent assay) were assessed. The production of reactive oxygen species (ROS) and nuclear factor (NF)-κB activation (translocation to the nuclei) in response to TNF-α stimulation was evaluated using fluorescence microscopy in the presence or absence of the inhibitors of mitochondrial electron flow and NF-κB activation. Stimulation of RGM-1 cells with TNF-α resulted in an increase in intracellular oxidative stress, NF-κB translocation to the nuclei, and up-regulation of CINC-1 mRNA and protein, which was prevented by interfering with mitochondria-dependent ROS production and NF-κB activation. Taken together, these findings indicate that CINC-1, a counterpart of the human GRO, production by rat gastric epithelial cells in response to TNF-α stimulation is an oxidant stress-mediated and NF-κB-dependent event. The American Society for Pharmacology and Experimental Therapeutics