NDLI: Helicobacter pylori infection activates Src homology-2 domain-containing phosphatase 2 to suppress IFN-Î³ signaling.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Hsieh, Chia-Yuan Tseng, Po-Chun Wang, Yu-Chih Chen, Chia-Ling Sheu, Bor-Shyang Yang, Yao-Jong Lin, Chiou-Feng
Description	Author Affiliation: Wang YC ( Institute of Clinical Medicine, College of Medicine, National Cheng Kung University, Tainan 701, Taiwan); Chen CL ( Center of Translational Medicine, Taipei Medical University, Taipei 110, Taiwan); Sheu BS ( Department of Internal Medicine, College of Medicine, National Cheng Kung University, Tainan 701, Taiwan); Yang YJ ( Department of Internal Medicine, College of Medicine, National Cheng Kung University, Tainan 701, Taiwan); Tseng PC ( Institute of Clinical Medicine, College of Medicine, National Cheng Kung University, Tainan 701, Taiwan); Hsieh CY ( Institute of Clinical Medicine, College of Medicine, National Cheng Kung University, Tainan 701, Taiwan); Lin CF ( Institute of Clinical Medicine, College of Medicine, National Cheng Kung University, Tainan 701, Taiwan)
Abstract	Helicobacter pylori infection not only induces gastric inflammation but also increases the risk of gastric tumorigenesis. IFN-Î³ has antimicrobial effects; however, H. pylori infection elevates IFN-Î³-mediated gastric inflammation and may suppress IFN-Î³ signaling as a strategy to avoid immune destruction through an as-yet-unknown mechanism. This study was aimed at investigating the mechanism of H. pylori-induced IFN-Î³ resistance. Postinfection of viable H. pylori decreased IFN-Î³-activated signal transducers and activators of transcription 1 and IFN regulatory factor 1 not only in human gastric epithelial MKN45 and AZ-521 but also in human monocytic U937 cells. H. pylori caused an increase in the C-terminal tyrosine phosphorylation of Src homology-2 domain-containing phosphatase (SHP) 2. Pharmacologically and genetically inhibiting SHP2 reversed H. pylori-induced IFN-Î³ resistance. In contrast to a clinically isolated H. pylori strain HP238, the cytotoxin-associated gene A (CagA) isogenic mutant strain HP238(CagAm) failed to induce IFN-Î³ resistance, indicating that CagA regulates this effect. Notably, HP238 and HP238(CagAm) differently caused SHP2 phosphorylation; however, imaging and biochemical analyses demonstrated CagA-mediated membrane-associated binding with phosphorylated SHP2. CagA-independent generation of reactive oxygen species (ROS) contributed to H. pylori-induced SHP2 phosphorylation; however, ROS/SHP2 mediated IFN-Î³ resistance in a CagA-regulated manner. This finding not only provides an alternative mechanism for how CagA and ROS coregulate SHP2 activation but may also explain their roles in H. pylori-induced IFN-Î³ resistance.
ISSN	00221767
e-ISSN	15506606
Journal	The Journal of Immunology
Issue Number	8
Volume Number	193
Language	English
Publisher	The American Association of Immunologists
Publisher Date	2014-10-15
Publisher Place	United States
Access Restriction	Open
Subject Keyword	Antigens, Bacterial Immunology Bacterial Proteins Helicobacter Infections Helicobacter Pylori Interferon-gamma Protein Tyrosine Phosphatase, Non-receptor Type 11 Animals Genetics Carcinogenesis Cell Line, Tumor Gastric Mucosa Microbiology Inflammation Interferon Regulatory Factor-1 Metabolism Antagonists & Inhibitors Mice Mice, Inbred C57bl Phosphorylation Rna Interference Rna, Small Interfering Reactive Oxygen Species Stat1 Transcription Factor U937 Cells Research Support, Non-u.s. Gov't Discipline Immunology
Content Type	Text
Resource Type	Article
Subject	Immunology and Allergy Immunology

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