Helicobacter pylori Induces IL-33 Production and Recruits ST-2 to Lipid Rafts to Exacerbate Inflammation

Cells

Chia-Jung Kuo¹  Tung-Nan Liao²  Horng-Ren Lo³  Chun-Ya Chen⁴  Mei-Zi Huang⁴  Hui-Yu Wu⁴  Yu-An Chen⁴  Chih-Ho Lai⁴  Chun-Lung Feng⁵ 

[1] Department of Gastroenterology and Hepatology, Chang Gung Memorial Hospital at Linkou, Taoyuan 33305, Taiwan;Department of Medical Laboratory Science and Biotechnology, Chung Hwa University of Medical Technology, Tainan 71703, Taiwan;Department of Medical Laboratory Science and Biotechnology, Fooyin University, Kaohsiung 83102, Taiwan;Department of Microbiology and Immunology, Graduate Institute of Biomedical Sciences, College of Medicine, Chang Gung University, Taoyuan 33302, Taiwan;Division of Gastroenterology and Hepatology, Department of Internal Medicine, China Medical University Hsinchu Hospital, Hsinchu 30272, Taiwan;

关键词: helicobacter pylori;    il-33;    st-2;    inflammation;    lipid rafts;   

DOI  :  10.3390/cells8101290

来源: DOAJ

【 摘 要 】

Helicobacter pylori colonizes human gastric epithelial cells and contributes to the development of several gastrointestinal disorders. Interleukin (IL)-33 is involved in various immune responses, with reported proinflammatory and anti-inflammatory effects, which may be associated with colitis and colitis-associated cancer. IL-33 induces the inflammatory cascade through its receptor, suppression of tumorigenicity-2 (ST-2). Binding of IL-33 to membrane-bound ST-2 (mST-2) recruits the IL-1 receptor accessory protein (IL-1RAcP) and activates intracellular signaling pathways. However, whether IL-33/ST-2 is triggered by H. pylori infection and whether this interaction occurs in lipid rafts remain unclear. Our study showed that both IL-33 and ST-2 expression levels were significantly elevated in H. pylori-infected cells. Confocal microscopy showed that ST-2 mobilized into the membrane lipid rafts during infection. Depletion of membrane cholesterol dampened H. pylori-induced IL-33 and IL-8 production. Furthermore, in vivo studies revealed IL-33/ST-2 upregulation, and severe leukocyte infiltration was observed in gastric tissues infected with H. pylori. Together, these results demonstrate that ST-2 recruitment into the lipid rafts serves as a platform for IL-33-dependent H. pylori infection, which aggravates inflammation in the stomach.

【 授权许可】

Unknown