Yonsei Med J.  2016 Jan;57(1):260-264. 10.3349/ymj.2016.57.1.260.

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

Affiliations
  • 1Department of Food and Nutrition, Brain Korea 21 PLUS Project, College of Human Ecology, Yonsei University, Seoul, Korea. kim626@yonsei.ac.kr
  • 2Department of Pharmacology, Yonsei University College of Medicine, Seoul, Korea.

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.

Keyword

alpha-lipoic acid; Helicobacter pylori; IL-8; NF-kappaB; MAPK; Jak/Stat

MeSH Terms

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
JNK Mitogen-Activated Protein Kinases
Janus Kinase 1
Interleukin-8
Mitogen-Activated Protein Kinases
NF-kappa B
RNA, Messenger
Reactive Oxygen Species
STAT3 Transcription Factor
Thioctic Acid
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