摘要
Intragastric growth of Helicobacter pylori and non-Helicobacter microorganisms is thought to be associated with elevated levels of pro-inflammatory cytokines and the production of NO these effects can lead to chronic inflammation. Microorganisms can activate the expression of iNOS and the production of NO by macrophages through stimulation with bacterial LPS. Helicobacter pylori can evade these vigorous immune responses, but the underlying mechanism remains unknown. In this study, we used a murine model of macrophage infection to demonstrate that H. pylori inhibits LPS-induced expression of iNOS and production of NO by macrophages. Suppression of LPS-induced NO production by macrophages led to elevated survival of H. pylori in a trans-well system. This effect was abrogated in macrophages from iNOS-/- mice. Analysis of iNOS mRNA and protein levels revealed that H. pylori inhibits iNOS expression at both transcriptional and post-transcriptional levels, and that these effects occurred with live bacteria. Furthermore, the effect of H. pylori involved down-regulation of the mitogen-activated protein kinase pathway and the translocation of active NF-κB into the nucleus. Taken together, our results reveal a new mechanism by which H. pylori modulates the innate immune responses of the host and maintains a persistent infection within the stomach.
| 原文 | 英語 |
|---|---|
| 頁（從 - 到） | 406-417 |
| 頁數 | 12 |
| 期刊 | Innate Immunity |
| 卷 | 18 |
| 發行號 | 3 |
| DOIs | |
| 出版狀態 | 已發佈 - 六月 2012 |
指紋
ASJC Scopus subject areas
- Cell Biology
- Molecular Biology
- Immunology
- Microbiology
- Infectious Diseases
引用此文
Helicobacter pylori attenuates lipopolysaccharide-induced nitric oxide production by murine macrophages. / Lu, Dah Yuu; Tang, Chin Hsin; Chang, Chia Hsian; Maa, Ming Chei; Fang, Shih Hua; Hsu, Yuan Man; Lin, Yu Hsin; Lin, Chun Jung; Lee, Wan Chi; Lin, Hwai Jeng; Lee, Che Hsin; Lai, Chih Ho.
於: Innate Immunity, 卷 18, 編號 3, 06.2012, p. 406-417.研究成果: 雜誌貢獻 › 文章
}
TY - JOUR
T1 - Helicobacter pylori attenuates lipopolysaccharide-induced nitric oxide production by murine macrophages
AU - Lu, Dah Yuu
AU - Tang, Chin Hsin
AU - Chang, Chia Hsian
AU - Maa, Ming Chei
AU - Fang, Shih Hua
AU - Hsu, Yuan Man
AU - Lin, Yu Hsin
AU - Lin, Chun Jung
AU - Lee, Wan Chi
AU - Lin, Hwai Jeng
AU - Lee, Che Hsin
AU - Lai, Chih Ho
PY - 2012/6
Y1 - 2012/6
N2 - Intragastric growth of Helicobacter pylori and non-Helicobacter microorganisms is thought to be associated with elevated levels of pro-inflammatory cytokines and the production of NO these effects can lead to chronic inflammation. Microorganisms can activate the expression of iNOS and the production of NO by macrophages through stimulation with bacterial LPS. Helicobacter pylori can evade these vigorous immune responses, but the underlying mechanism remains unknown. In this study, we used a murine model of macrophage infection to demonstrate that H. pylori inhibits LPS-induced expression of iNOS and production of NO by macrophages. Suppression of LPS-induced NO production by macrophages led to elevated survival of H. pylori in a trans-well system. This effect was abrogated in macrophages from iNOS-/- mice. Analysis of iNOS mRNA and protein levels revealed that H. pylori inhibits iNOS expression at both transcriptional and post-transcriptional levels, and that these effects occurred with live bacteria. Furthermore, the effect of H. pylori involved down-regulation of the mitogen-activated protein kinase pathway and the translocation of active NF-κB into the nucleus. Taken together, our results reveal a new mechanism by which H. pylori modulates the innate immune responses of the host and maintains a persistent infection within the stomach.
AB - Intragastric growth of Helicobacter pylori and non-Helicobacter microorganisms is thought to be associated with elevated levels of pro-inflammatory cytokines and the production of NO these effects can lead to chronic inflammation. Microorganisms can activate the expression of iNOS and the production of NO by macrophages through stimulation with bacterial LPS. Helicobacter pylori can evade these vigorous immune responses, but the underlying mechanism remains unknown. In this study, we used a murine model of macrophage infection to demonstrate that H. pylori inhibits LPS-induced expression of iNOS and production of NO by macrophages. Suppression of LPS-induced NO production by macrophages led to elevated survival of H. pylori in a trans-well system. This effect was abrogated in macrophages from iNOS-/- mice. Analysis of iNOS mRNA and protein levels revealed that H. pylori inhibits iNOS expression at both transcriptional and post-transcriptional levels, and that these effects occurred with live bacteria. Furthermore, the effect of H. pylori involved down-regulation of the mitogen-activated protein kinase pathway and the translocation of active NF-κB into the nucleus. Taken together, our results reveal a new mechanism by which H. pylori modulates the innate immune responses of the host and maintains a persistent infection within the stomach.
KW - Helicobacter pylori
KW - Lipopolysaccharide
KW - macrophage
KW - NF-κB
KW - nitric oxide
UR - http://www.scopus.com/inward/record.url?scp=84861802578&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84861802578&partnerID=8YFLogxK
U2 - 10.1177/1753425911413164
DO - 10.1177/1753425911413164
M3 - Article
C2 - 21926162
AN - SCOPUS:84861802578
VL - 18
SP - 406
EP - 417
JO - Innate Immunity
JF - Innate Immunity
SN - 1753-4259
IS - 3
ER -