Astaxanthin Inhibits Mitochondrial Dysfunction and Interleukin-8 Expression in Helicobacter pylori-Infected Gastric Epithelial Cells.

Suhn Kim,Hyeyoung Kim,Joo Lim

doi:10.3390/nu10091320

Abstract

Helicobacter pylori (H. pylori) infection leads to gastric inflammation, peptic ulcer and gastric carcinoma. H. pylori activates NADPH oxidase and increases reactive oxygen species (ROS), which induce NF-κB activation and IL-8 expression in gastric epithelial cells. Dysfunctional mitochondria trigger inflammatory cytokine production. Peroxisome proliferator-activated receptors-γ (PPAR-γ) regulate inflammatory response. Astaxanthin is a powerful antioxidant that protects cells against oxidative stress. The present study was aimed at determining whether astaxanthin inhibits H. pylori-induced mitochondrial dysfunction, NF-κB activation, and IL-8 expression via PPAR-γ activation in gastric epithelial cells. Gastric epithelial AGS cells were treated with astaxanthin, NADPH oxidase inhibitor apocynin and PPAR-γ antagonist GW9662, and infected with H. pylori. As a result, H. pylori caused an increase in intracellular and mitochondrial ROS, NF-κB activation and IL-8 expression, but decreased mitochondrial membrane potential and ATP level. Astaxanthin inhibited H. pylori-induced alterations (increased ROS, mitochondrial dysfunction, NF-κB activation, and IL-8 expression). Astaxanthin activated PPAR-γ and its target gene catalase in H. pylori-infected cells. Apocynin reduced ROS and inhibited IL-8 expression while astaxanthin did not affect NADPH oxidase activity. Inhibitory effects of astaxanthin on ROS levels and IL-8 expression were suppressed by addition of GW9662. In conclusion, astaxanthin inhibits H. pylori-induced mitochondrial dysfunction and ROS-mediated IL-8 expression by activating PPAR-γ and catalase in gastric epithelial cells. Astaxanthin may be beneficial for preventing oxidative stress-mediated gastric inflammation-associated H. pylori infection.

Highlights

Helicobacter pylori (H. pylori) is a Gram-negative, microaerophilic bacterium that infects more than half of the world’s human population
H. pylori-induced IL-8 gene expression was inhibited by apocynin (Figure 3C,D). These results demonstrate that Nicotinamide adenine dinucleotide phosphate (NADPH) oxidase contributes to increases in both intracellular and mitochondrial reactive oxygen species (ROS) levels, and to IL-8 gene expression in H. pylori-infected cells
“Control” vs. “None”), and pretreatment with astaxanthin had no effect on this increase. These results show that the inhibitory effect of astaxanthin on ROS levels and IL-8 expression is not the result of NADPH oxidase inhibition

Summary

Introduction

Helicobacter pylori (H. pylori) is a Gram-negative, microaerophilic bacterium that infects more than half of the world’s human population. H. pylori infection can cause chronic inflammation of the stomach, and result in gastritis, peptic ulcers, mucosa-associated lymphoid tissue lymphoma and gastric carcinoma [1]. In 1984, Marshall and Warren were the first to discover H. pylori in gastritis and peptic ulcer patients and to identify this pathogen as being causally associated with gastric diseases [2]. H. pylori stimulates cytokine release and activation of inflammatory mediators [3]. Upregulation of the inflammatory chemokine interleukin-8 (IL-8) is pronounced in H. pylori-infected patients who manifest high levels of IL-8 in their gastric mucosa [4]. Increased IL-8 in gastric mucosa is associated with severe chronic gastritis and active progression of gastric cancer [5]. IL-8 recruits neutrophils to the site of infection and stimulates the generation of reactive oxygen species (ROS) [6]

Results

Discussion

Conclusion