Tumor necrosis factor-alpha-induced cytokine-induced neutrophil chemoattractant-1 (CINC-1) production by rat gastric epithelial cells: role of reactive oxygen species and nuclear factor-kappaB.

Abstract

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)-alpha, 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)-kappaB activation (translocation to the nuclei) in response to TNF-alpha stimulation was evaluated using fluorescence microscopy in the presence or absence of the inhibitors of mitochondrial electron flow and NF-kappaB activation. Stimulation of RGM-1 cells with TNF-alpha resulted in an increase in intracellular oxidative stress, NF-kappaB 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-kappaB 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-alpha stimulation is an oxidant stress-mediated and NF-kappaB-dependent event.

• Authors: Osamu Handa, Yuji Naito, Tomohisa Takagi, Makoto Shimozawa, Satoshi Kokura, Norimasa Yoshida, Hirofumi Matsui, Gediminas Cepinskas, Peter R Kvietys, Toshikazu Yoshikawa
• Journal: The Journal of pharmacology and experimental therapeutics (J Pharmacol Exp Ther) Vol. 309 Issue 2 Pg. 670-6 (May 2004) ISSN: 0022-3565 [Print] United States
• PMID: 14747614 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Chemokine CXCL1
• Chemokines, CXC
• Cxcl1 protein, rat
• Cytokines
• Intercellular Signaling Peptides and Proteins
• NF-kappa B
• RNA, Messenger
• Reactive Oxygen Species
• Tumor Necrosis Factor-alpha

Topics

• Animals
• Chemokine CXCL1
• Chemokines, CXC (genetics, metabolism)
• Cytokines (pharmacology)
• Gastric Mucosa (drug effects, metabolism)
• Humans
• Intercellular Signaling Peptides and Proteins (genetics, metabolism)
• NF-kappa B (antagonists & inhibitors, metabolism)
• Oxidative Stress (drug effects)
• RNA, Messenger (drug effects, metabolism)
• Rats
• Reactive Oxygen Species (metabolism)
• Time Factors
• Tumor Necrosis Factor-alpha (pharmacology)