RRC ID 42082
Author Handa O, Naito Y, Takagi T, Shimozawa M, Kokura S, Yoshida N, Matsui H, Cepinskas G, Kvietys PR, Yoshikawa T.
Title 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.
Journal J Pharmacol Exp Ther
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.
Volume 309(2)
Pages 670-6
Published 2004-5-1
DOI 10.1124/jpet.103.062216
PII jpet.103.062216
PMID 14747614
MeSH Animals Chemokine CXCL1 Chemokines, CXC / genetics Chemokines, CXC / metabolism* Cytokines / pharmacology Gastric Mucosa / drug effects* Gastric Mucosa / metabolism Humans Intercellular Signaling Peptides and Proteins / genetics Intercellular Signaling Peptides and Proteins / metabolism* NF-kappa B / antagonists & inhibitors NF-kappa B / metabolism* Oxidative Stress / drug effects RNA, Messenger / drug effects RNA, Messenger / metabolism Rats Reactive Oxygen Species / metabolism* Time Factors Tumor Necrosis Factor-alpha / pharmacology*
IF 3.561
Times Cited 52
WOS Category PHARMACOLOGY & PHARMACY
Resource
Human and Animal Cells RGM1(RCB0876)