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

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

The Expression of Heme Oxygenase-1 Induced by Lansoprazole

“…In addition to its acid-suppressing effects, lansoprazole have been shown to modulate the inflammatory status, reduce oxidative stress, and ameliorate mucosal injuries in the esophagus [23,24], intestine [25,26], and lung [27], in addition to the stomach [28,29]. It has been also demonstrated by in vitro studies that lansoprazole inhibits the increased expression of vascular adhesion molecules, the activation of neutrophils, and the production of pro-inflammatory cytokines from activated endothelial cells [30,31]. We recently demonstrated using in vivo models that lansoprazole inhibits acute inflammatory reactions as well as intestinal mucosal injuries induced by ischemia-reperfusion [25] or indomethacin administration in rats [26].…”

“…Our previous report demonstrated that rat gastric epithelial cells (RGM-1 cells) produced CINC-1 in response to various pro-inflammatory cytokines, such as TNF-α, IL-1β, and bacterial LPS [30]. To confirm the anti-inflammatory effect of lansoprazole-induced HO-1 on RGM-1 cells, we measured the production of CINC-1 on RGM-1 cells using ELISA.…”

Bile Acid Promotes Intestinal Metaplasia and Gastric Carcinogenesis

“…Cytokineinduced neutrophil chemoattractant-1 (CINC1), which corresponds to human interleukin-8 (IL-8), is a key cytokine in the rat. Previous studies showed that CINC1 protein plays an important role in rat gastric inflammation induced by H. pylori infection (17).…”

Rat Cytokine-Induced Neutrophil Chemoattractant-1 (CINC-1) in Inflammation

“…Based on their findings, they speculated that the oxygen radicals produced following I/R of the liver stimulate Kupffer cells to release CINC-1. We have shown direct evidence of the involvement of ROS in the signaling pathway of CINC-1 production in an in vitro model of gastric inflammation: in which we demonstrated that TNF-α-induced CINC-1 production in a rat gastric mucosal cell line (RGM-1) is an event mediated by oxidative stress and is dependent on NFκB activation [37].…”