J Cancer 2018; 9(15):2757-2764. doi:10.7150/jca.26083

Research Paper

Involvement of Aryl Hydrocarbon Receptor and Aryl Hydrocarbon Receptor Repressor in Helicobacter Pylori-related Gastric Pathogenesis

Renfei Zhu1,2*, Cheng Gao1*, Liuhua Wang1*, Guoxin Zhang3, Weiming Zhang4, Zhihong Zhang4, Lizong Shen1✉, Shoulin Wang5✉

1. Division of Gastrointestinal Surgery, Department of General Surgery, First Affiliated Hospital, Nanjing Medical University, Nanjing 210029, China
2. Department of Hepatobiliary Surgery, Third People's Hospital of Nantong, Nantong 226000, China
3. Department of Gastroenterology, First Affiliated Hospital, Nanjing Medical University, Nanjing 210029, China
4. Department of Pathology, First Affiliated Hospital, Nanjing Medical University, Nanjing 210029, China
5. School of Public Health, Nanjing Medical University, Nanjing 211166, China
*These authors contributed equally to this work.

Abstract

Background: Persistent Helicobacter pylori (H. pylori) infection leads to various gastric diseases. Multiple studies have demonstrated that aryl hydrocarbon receptor (AHR) plays roles in the antibacterial response and aryl hydrocarbon receptor repressor (AHRR) is downregulated in stomach cancer. However, the role of AHR or AHRR in H. pylori-related gastric diseases remains unclear.

Aims: To investigate whether AHR or AHRR is involved in H. pylori-related gastric diseases.

Methods: Patients with gastritis or gastric adenocarcinoma were enrolled randomly, and gastric tissue specimens were diagnosed pathologically. AHR, AHRR, and H. pylori infection status in tissues were detected by immunohistochemistry. Human gastric cells were cocultured with H. pylori. siRNAs were used to silence AHR or AHRR, and a C57bl/6 mouse model colonized by H. pylori was established. Protein expression was determined by western blotting analysis, and TNF, IL-8 and IL-1β in cell supernatants were measured by ELISA.

Results: AHR and AHRR were expressed in gastritis tissues and gastric cancer tissues without H. pylori infection, and principally located in the cytoplasm and nucleus. AHR expression was significantly correlated with AHRR expression in gastric tissues without H. pylori infection (P=0.008). However, their expressions were negatively correlated with H. pylori infection status. H. pylori coculture inhibited AHR and AHRR expression in stomach mucosa in vitro and in vivo. Gastric cells produced more TNF, IL-8 and IL-1β when AHR or AHRR was silenced.

Conclusions: This preliminary study indicates that AHR and AHRR may be involved in H. pylori-related gastric pathogenesis, and helps toward understanding of inflammation-initiated carcinogenesis of gastric cancer.

Keywords: aryl hydrocarbon receptor, aryl hydrocarbon receptor repressor, H. pylori, gastric cancer

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How to cite this article:
Zhu R, Gao C, Wang L, Zhang G, Zhang W, Zhang Z, Shen L, Wang S. Involvement of Aryl Hydrocarbon Receptor and Aryl Hydrocarbon Receptor Repressor in Helicobacter Pylori-related Gastric Pathogenesis. J Cancer 2018; 9(15):2757-2764. doi:10.7150/jca.26083. Available from http://www.jcancer.org/v09p2757.htm