Abstract
Helicobacter pylori causes gastrointestinal diseases, the manifestations of diseases are more serious in adults than in children. Lewis antigen expressions on the gastric epithelium serves as receptors targeted by H. pylori. Moreover, the MAPK signaling pathway involves glycoprotein synthesis of Lewis antigens. We aimed to investigate whether differences in H. pylori-induced MAPK responses mediate gastric Lewis antigens expression and colonization density differently in children and adults. We used human stomach fetal epithelium (HSFE) and SV40-immortalized human normal gastric epithelial (GES-1) cell lines to mimic primary gastric epithelium of children and adults, respectively. H. pylori colonization intensity and Lewis antigens were significantly higher in GES-1 than in HSFE cells, whereas IL-8 and IL-6 levels were significantly higher in HSFE than in GES-1 cells after infection. c-Jun N-terminal kinase (JNK) siRNA and inhibitor (SP600125) experiments showed that Lewis antigen expression and H. pylori colonization were reduced in GES-1 cells but increased in HSFE cells. Furthermore, p-p38 intensity was significantly higher in the superficial epithelium of the children than in the adults with/without H. pylori infection. The overexpression of p38 in GES-1 cells downregulated H. pylori-induced JNK activity mimicking H. pylori infection in children. In conclusion, a higher p38 expression in gastric epithelium counteracting JNK activity in children may contribute to lower Lewis antigen expression and colonization density than in adults after H. pylori infection.
Highlights
Helicobacter pylori infection causes chronic gastritis, peptic ulcer disease, and adenocarcinoma in humans [1, 2]
As p-Jun N-terminal kinase (JNK) activity was shown to have the greatest impact on the difference in H. pylori colonization density between the GES-1 and human stomach fetal epithelium (HSFE) cells, we further investigated whether p-JNK activity affected differences in Lewis antigen expressions between the GES-1 and HSFE cells using siRNA and a p-JNK inhibitor (Figures 6A, B)
We found that H. pylori induced JNK phosphorylation in vivo and in vitro, which upregulated the expressions of gastric Lewis antigens and subsequent bacterial colonization density
Summary
Helicobacter pylori infection causes chronic gastritis, peptic ulcer disease, and adenocarcinoma in humans [1, 2]. The cross-talk of bacteria and host immunity mediates the pathogenesis of subsequent disease [3], and the adhesion and colonization of H. pylori to the gastric epithelium is the key step in establishing the infectious process [4, 5]. Adhesion molecules such as BabA and SabA proteins are produced by H. pylori and have been shown to adhere to the glycan-rich domains of the gastric epithelium [5–7]. The BabA protein recognizes both H-type 1 and Lewis b (Leb) antigens expressed on gastric mucosa leading to the initial step of infection [5]. Factors that can regulate the intensity of Lewis antigens are responsible for H. pylori colonization density on the gastric epithelium
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