Abstract
Sepsis, a systemic inflammatory response syndrome caused by infection, is the most common disease in patients treated in intensive care units. Endotoxic shock, the most critical form of sepsis, is caused by gram-negative bacterial infection. However, the detailed mechanism of endotoxic shock remains unclear. In the present study, we observed that the production of leukotriene B 4 (LTB 4 ) and 12(S)-hydroxyeicosatetraenoic acid (HETE), inflammatory lipid mediators acting on LTB 4 receptors (BLT1 and BLT2), was significantly upregulated in peritoneal lavage fluid (PF) and serum from an LPS-induced endotoxic shock mouse model. Furthermore, BLT1/2-dependent signaling pathways mediated the expression of IL-17, IL-6, and IL-1β, key cytokines for the development of endotoxic shock, via NF-κB activation in the LPS-induced endotoxic shock mouse model. Additionally, inhibition of BLT1/2 significantly attenuated inflammation and tissue damage associated with endotoxic shock and enhanced the survival rate of mice with this inflammatory complication. Together, these results suggest that LTB 4 receptors play critical mediatory roles in the development of endotoxic shock. Our findings point to LTB 4 receptors as potential therapeutic targets for the treatment of endotoxic shock.
Original language | English |
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Article number | 5936 |
Journal | Scientific reports |
Volume | 9 |
Issue number | 1 |
DOIs | |
Publication status | Published - 2019 Dec 1 |
Bibliographical note
Funding Information:This work was supported by Bio and Medical Technology Development Program grants (2017M3A9D8063317) and a Mid-Career Researcher Program grant (2017R1A2B4002203) through the National Research Foundation (NRF) funded by the Ministry of Science, Information and Communication Technologies (ICT), and Future Planning, Republic of Korea. This work was also supported by the BK21 Plus Program (College of Life Sciences and Biotechnology, Korea University), as well as by a Korea University Grant. Moreover, the authors thank the staff of Gyerim Experimental Animal Resource Center for animal care and technical assistance.
Publisher Copyright:
© 2019, The Author(s).
ASJC Scopus subject areas
- General