PT  - JOURNAL ARTICLE
AU  - Osamu Handa
AU  - Yuji Naito
AU  - Tomohisa Takagi
AU  - Makoto Shimozawa
AU  - Satoshi Kokura
AU  - Norimasa Yoshida
AU  - Hirofumi Matsui
AU  - Gediminas Cepinskas
AU  - Peter R. Kvietys
AU  - Toshikazu Yoshikawa
TI  - 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
AID  - 10.1124/jpet.103.062216
DP  - 2004 May 01
TA  - Journal of Pharmacology and Experimental Therapeutics
PG  - 670--676
VI  - 309
IP  - 2
4099  - http://jpet.aspetjournals.org/content/309/2/670.short
4100  - http://jpet.aspetjournals.org/content/309/2/670.full
SO  - J Pharmacol Exp Ther2004 May 01; 309
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