https://scholars.lib.ntu.edu.tw/handle/123456789/504024
標題: | Monocytic thrombomodulin triggers LPS- and gram-negative bacteria-induced inflammatory response | 作者: | Ma C.-Y. Shi G.-Y. Shi C.-S. Kao Y.-C. SHU-WHA LIN Wu H.-L. |
公開日期: | 2012 | 卷: | 188 | 期: | 12 | 起(迄)頁: | 6328_6337 | 來源出版物: | Journal of Immunology | 摘要: | Sepsis results from the host hyperinflammatory response to bacterial infection, causing multiple organ failure and high mortality. We previously demonstrated that LPS binds to monocytic membrane-bound thrombomodulin (TM), but the role of monocytic TM in LPS-induced inflammation remains unknown. In this study, we demonstrated that TM knockdown in human monocytic cells attenuated LPS-induced signaling pathways and cytokine production. Coimmunoprecipitation and immunofluorescence assays showed that monocytic TM interacted with the LPS receptors, CD14 and TLR4/myeloid differentiation factor-2 (MD-2) complex, indicating that it binds to LPS and triggers an LPS-induced inflammatory response by interacting with the CD14/TLR4/MD-2 complex. We also found that monocytic TM knockdown reduced cytokine production induced by Gram-negative bacteria Klebsiella pneumoniae, suggesting that monocytic TM plays an important role in Gram-negative bacteria-induced inflammation. To further investigate the function of monocytic TM in vivo, myeloid-specific TM-deficient mice were established and were found to display improved survival that resulted from the attenuation of septic syndrome, including reduced systemic inflammatory response and resistance to bacterial dissemination, after K. pneumoniae infection or cecal ligation and puncture surgery. The inhibition of bacterial dissemination in mice with a deficiency of myeloid TM may be caused by the early increase in neutrophil infiltration. Therefore, we conclude that monocytic TM is a novel component in the CD14/TLR4/MD-2 complex and participates in the LPS- and Gram-negative bacteria-induced inflammatory response. Copyright ? 2012 by The American Association of Immunologists, Inc. |
URI: | https://scholars.lib.ntu.edu.tw/handle/123456789/504024 | ISSN: | 0022-1767 | DOI: | 10.4049/jimmunol.1102266 | SDG/關鍵字: | CD14 antigen; cre recombinase; interleukin 1beta; interleukin 6; lectin; lipopolysaccharide; mitogen activated protein kinase 1; protein MD 2; thrombomodulin; toll like receptor 4; tumor necrosis factor alpha; animal cell; animal experiment; animal model; article; colony forming unit; complex formation; controlled study; cytokine production; dose response; down regulation; enzyme phosphorylation; Gram negative bacterium; Gram negative sepsis; immunofluorescence; immunoprecipitation; inflammation; Klebsiella pneumoniae; Klebsiella pneumoniae infection; monocyte; mouse; neutrophil chemotaxis; nonhuman; priority journal; protein expression; protein protein interaction; RNA interference; signal transduction; systemic inflammatory response syndrome; Animals; Cell Line; Cytokines; Flow Cytometry; Fluorescent Antibody Technique; Gene Knockdown Techniques; Gram-Negative Bacterial Infections; Humans; Immunoprecipitation; Inflammation; Lipopolysaccharides; Mice; Monocytes; Reverse Transcriptase Polymerase Chain Reaction; Sepsis; Thrombomodulin |
顯示於: | 醫學檢驗暨生物技術學系 |
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