Molecules and Cells

Korean Society for Molecular and Cellular Biology (한국분자세포생물학회)
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Contributory Role of BLT2 in the Production of Proinflammatory Cytokines in Cecal Ligation and Puncture-Induced Sepsis

  • Park, Donghwan (Department of Biotechnology, College of Life Sciences, Korea University) ;
  • Ro, MyungJa (Department of Biotechnology, College of Life Sciences, Korea University) ;
  • Lee, A-Jin (Department of Biotechnology, College of Life Sciences, Korea University) ;
  • Kwak, Dong-Wook (Department of Biotechnology, College of Life Sciences, Korea University) ;
  • Chung, Yunro (College of Health Solutions, Arizona State University) ;
  • Kim, Jae-Hong (Division of Life Sciences, College of Life Sciences, Korea University)
  • Received : 2021.06.17
  • Accepted : 2021.10.15
  • Published : 2021.12.31
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Abstract

BLT2 is a low-affinity receptor for leukotriene B4, a potent lipid mediator of inflammation generated from arachidonic acid via the 5-lipoxygenase pathway. The aim of this study was to investigate whether BLT2 plays any role in sepsis, a systemic inflammatory response syndrome caused by infection. A murine model of cecal ligation and puncture (CLP)-induced sepsis was used to evaluate the role of BLT2 in septic inflammation. In the present study, we observed that the levels of ligands for BLT2 (LTB4 [leukotriene B4] and 12(S)-HETE [12(S)-hydroxyeicosatetraenoic acid]) were significantly increased in the peritoneal lavage fluid and serum from mice with CLP-induced sepsis. We also observed that the levels of BLT2 as well as 5-lipoxygenase (5-LO) and 12-LO, which are synthesizing enzymes for LTB4 and 12(S)-HETE, were significantly increased in lung and liver tissues in the CLP mouse model. Blockade of BLT2 markedly suppressed the production of sepsis-associated cytokines (IL-6 [interleukin-6], TNF-α [tumor necrosis factor alpha], and IL-1β [interleukin-β] as well as IL-17 [interleukin-17]) and alleviated lung inflammation in the CLP group. Taken together, our results suggest that BLT2 cascade contributes to lung inflammation in CLP-induced sepsis by mediating the production of inflammatory cytokines. These findings suggest that BLT2 may be a potential therapeutic target for sepsis patients.

Keywords

Acknowledgement

This work was supported by a Bio & Medical Technology Development Program Grant (2017M3A9D8063317) and a Mid-Career Researcher Program Grant (2020R1A2B5B01002046) through the National Research Foundation funded by the Ministry of Science, Information and Communication Technologies (ICT), and Future Planning, Republic of Korea. This work was also supported by a Korea University Grant.

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