Contributory Role of BLT2 in the Production of Proinflammatory Cytokines in Cecal Ligation and Puncture-Induced Sepsis |
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Authors: | Donghwan Park MyungJa Ro A-Jin Lee Dong-Wook Kwak Yunro Chung Jae-Hong Kim |
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Institution: | 1.Department of Biotechnology, College of Life Sciences, Korea University, Seoul 02841, Korea;2.College of Health Solutions, Arizona State University, Phoenix, AZ 85004, USA;3.Biodesign Center for Personalized Diagnostics, Arizona State University, Tempe, AZ 85281, USA;4.Division of Life Sciences, College of Life Sciences, Korea University, Seoul 02841, Korea |
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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-αtumor necrosis factor alpha], and IL-1β interleukin-1β] 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. |
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Keywords: | BLT2 cecal ligation and puncture cytokines leukotrienes sepsis |
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