Monocytic thrombomodulin triggers LPS- and gram-negative bacteria-induced inflammatory response

The Journal of Immunology : Official Journal of the American Association of Immunologists
Chih-Yuan MaHua-Lin Wu

Abstract

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 t...Continue Reading

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Citations

Nov 4, 2016·Immunology and Cell Biology·Wei-Ling LinHua-Lin Wu
Feb 6, 2017·Biological & Pharmaceutical Bulletin·Yadan ZhangMing Jin
Jun 6, 2018·Blood·Houra Loghmani, Edward M Conway
Sep 5, 2015·Arteriosclerosis, Thrombosis, and Vascular Biology·Kuan-Chieh WangHua-Lin Wu
Oct 21, 2018·Journal of Molecular Medicine : Official Organ of the Gesellschaft Deutscher Naturforscher Und Ärzte·Tsung-Lin ChengChao-Han Lai
Jan 23, 2015·The Journal of Immunology : Official Journal of the American Association of Immunologists·Chih-Yuan MaHua-Lin Wu
Apr 25, 2020·Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research·Chung-Hwan ChenTsung-Lin Cheng
Apr 9, 2020·International Journal of Molecular Sciences·Yuji NozakiItaru Matsumura
Apr 25, 2020·Nutrients·Oona KoivistoCarsten Carlberg

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