Bibliographic Details
| Title: |
Abrogation of cathepsin C by Helicobacter pylori impairs neutrophil activation to promote gastric infection. |
| Authors: |
Yu Gang Liu1, Yong Sheng Teng1, Ping Cheng1, Hui Kong1, Yi Pin Lv1, Fang Yuan Mao1, Xiao Long Wu1, Chuan Jie Hao1, Weisan Chen2, Shi Ming Yang3, Jin Yu Zhang1, Liu Sheng Peng1, Ting Ting Wang1, Bin Han4, Qiang Ma5, Quan Ming Zou1 qmzou@tmmu.edu.cn, Yuan Zhuang1 yuanzhuang1983@yahoo.com |
| Source: |
FASEB Journal. Apr2019, Vol. 33 Issue 4, p5018-5033. 16p. |
| Abstract: |
Cathepsin C (CtsC) functions as a central coordinator for activation of many serine proteases in immune cells. However, CtsC expression in gastric epithelial cells and its role in Helicobacter pylori infection remain unclear. Real-time PCR, Western blot, and immunohistochemistry analyses identified that CtsC was decreased in gastric mucosa of H. pylori-infected patients and mice. Isolated gastric epithelial cells and cell lines were stimulated with H. pylori and/or TGF-ß1 showed that down-regulation of CtsC in gastric epithelial cells largely depended on H. pylori cagAvia Src/ERK and Janus kinase (JAK)/signal transducer and activator of transcription 3 (STAT3) pathways, and the effect could be synergistically augmented by TGF-ß1 in an autocrine manner. In human gastric mucosa, CtsC expression was negatively correlated with bacteria colonization; accordingly, provision of exogenous active CtsC overwhelmed H. pylori persistence in gastric mucosa of mice. In the presence of active CtsC, isolated human neutrophils activated via NF-κB pathway with augmented bactericidal capacity in vitro. We also found that neutrophils activated and cleared bacteria in active CtsC-injected mice and that there was no bactericidal capacity in mice that were simultaneously neutrophil-depleted by Ly6G antibody. Our findings identified a mechanism that H. pylori abrogate CtsC to impair neutrophil activation and to ensure persistence in gastric mucosa. Efforts to enable and boost this neutrophil activation pathway by active CtsC may therefore become valuable strategies in treating H. pylori infection. [ABSTRACT FROM AUTHOR] |
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| Database: |
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