J Cancer Prev.  2015 Sep;20(3):179-184. 10.15430/JCP.2015.20.3.179.

Glutamine Deprivation Causes Hydrogen Peroxide-induced Interleukin-8 Expression via Jak1/Stat3 Activation in Gastric Epithelial AGS Cells

• Lee YM
• Kim MJ
• Kim Y
• Kim H

• KMID: 2380868
• DOI: http://doi.org/10.15430/JCP.2015.20.3.179

Abstract

BACKGROUND
The Janus kinase (Jak)/Signal transducers of activated transcription (Stat) pathway is an upstream signaling pathway for NF-kappaB activation in Helicobacter pylori-induced interleukin (IL)-8 production in gastric epithelial AGS cells. H. pylori activates NADPH oxidase and produces hydrogen peroxide, which activates Jak1/Stat3 in AGS cells. Therefore, hydrogen peroxide may be critical for IL-8 production via Jak/Stat activation in gastric epithelial cells. Glutamine is depleted during severe injury and stress and contributes to the formation of glutathione (GSH), which is involved in conversion of hydrogen peroxide into water as a cofactor for GSH peroxidase.
METHODS
We investigated whether glutamine deprivation induces hydrogen peroxide-mediated IL-8 production and whether hydrogen peroxide activates Jak1/Stat3 to induce IL-8 in AGS cells. Cells were cultured in the presence or absence of glutamine or hydrogen peroxide, with or without GSH or a the Jak/Stat specific inhibitor AG490.
RESULTS
Glutamine deprivation decreased GSH levels, but increased levels of hydrogen peroxide and IL-8, an effect that was inhibited by treatment with GSH. Hydrogen peroxide induced the activation of Jak1/Stat3 time-dependently. AG490 suppressed hydrogen peroxideinduced activation of Jak1/Stat3 and IL-8 expression in AGS cells, but did not affect levels of reactive oxygen species in AGS cells.
CONCLUSIONS
In gastric epithelial AGS cells, glutamine deprivation increases hydrogen peroxide levels and IL-8 expression, which may be mediated by Jak1/Stat3 activation. Glutamine supplementation may be beneficial for preventing gastric inflammation by suppressing hydrogen peroxide-mediated Jak1/Stat3 activation and therefore, reducing IL-8 production. Scavenging hydrogen peroxide or targeting Jak1/Stat3 may also prevent oxidant-mediated gastric inflammation.

Keyword

Glutamine; Hydrogen peroxide; Janus kinase; Interleukin-8; Signal transducers of activated transcription

MeSH Terms

Epithelial Cells
Glutamine*
Glutathione
Helicobacter
Hydrogen Peroxide
Hydrogen*
Inflammation
Interleukin-8*
Interleukins
NADPH Oxidase
NF-kappa B
Peroxidase
Phosphotransferases
Reactive Oxygen Species
Transducers
Water
Glutamine
Glutathione
Hydrogen
Hydrogen Peroxide
Interleukin-8
Interleukins
NADPH Oxidase
NF-kappa B
Peroxidase
Phosphotransferases
Reactive Oxygen Species
Water