alpha-Lipoic Acid Inhibits Expression of IL-8 by Suppressing Activation of MAPK, Jak/Stat, and NF-kappaB in H. pylori-Infected Gastric Epithelial AGS Cells.
10.3349/ymj.2016.57.1.260
- Author:
Ji Hyun CHOI
1
;
Soon Ok CHO
;
Hyeyoung KIM
Author Information
1. Department of Food and Nutrition, Brain Korea 21 PLUS Project, College of Human Ecology, Yonsei University, Seoul, Korea. kim626@yonsei.ac.kr
- Publication Type:Brief Communication ; Research Support, Non-U.S. Gov't
- Keywords:
alpha-lipoic acid;
Helicobacter pylori;
IL-8;
NF-kappaB;
MAPK;
Jak/Stat
- MeSH:
Enzyme-Linked Immunosorbent Assay;
Epithelial Cells/metabolism;
Gastric Mucosa/*drug effects/metabolism/microbiology;
Gene Expression Regulation, Bacterial;
Helicobacter Infections/immunology/*metabolism;
Helicobacter pylori/drug effects/*pathogenicity;
Humans;
Interleukin-8/genetics/*metabolism;
JNK Mitogen-Activated Protein Kinases;
Janus Kinase 1;
Mitogen-Activated Protein Kinases/*biosynthesis;
NF-kappa B/*metabolism;
RNA, Messenger/isolation & purification/metabolism;
Reactive Oxygen Species/metabolism;
STAT3 Transcription Factor;
Stomach/metabolism/*microbiology;
Thioctic Acid/*pharmacology
- From:Yonsei Medical Journal
2016;57(1):260-264
- CountryRepublic of Korea
- Language:English
-
Abstract:
The epithelial cytokine response, associated with reactive oxygen species (ROS), is important in Helicobacter pylori (H. pylori)-induced inflammation. H. pylori induces the production of ROS, which may be involved in the activation of mitogen-activated protein kinases (MAPK), janus kinase/signal transducers and activators of transcription (Jak/Stat), and oxidant-sensitive transcription factor, nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kappaB), and thus, expression of interleukin-8 (IL-8) in gastric epithelial cells. alpha-lipoic acid, a naturally occurring thiol compound, is a potential antioxidant. It shows beneficial effects in treatment of oxidant-associated diseases including diabetes. The present study is purposed to investigate whether alpha-lipoic acid inhibits expression of inflammatory cytokine IL-8 by suppressing activation of MAPK, Jak/Stat, and NF-kappaB in H. pylori-infected gastric epithelial cells. Gastric epithelial AGS cells were pretreated with or without alpha-lipoic acid for 2 h and infected with H. pylori in a Korean isolate (HP99) at a ratio of 300:1. IL-8 mRNA expression was analyzed by RT-PCR analysis. IL-8 levels in the medium were determined by enzyme-linked immunosorbent assay. NF-kappaB-DNA binding activity was determined by electrophoretic mobility shift assay. Phospho-specific and total forms of MAPK and Jak/Stat were assessed by Western blot analysis. ROS levels were determined using dichlorofluorescein fluorescence. As a result, H. pylori induced increases in ROS levels, mRNA, and protein levels of IL-8, as well as the activation of MAPK [extracellular signal-regulated kinase 1/2 (ERK1/2), c-Jun NH2-terminal kinase 1/2 (JNK1/2), p38], Jak/Stat (Jak1/2, Stat3), and NF-kappaB in AGS cells, which was inhibited by alpha-lipoic acid. In conclusion, alpha-lipoic acid may be beneficial for prevention and/or treatment of H. pylori infection-associated gastric inflammation.
