Contributory Role of BLT2 in the Production of Proinflammatory Cytokines in Cecal Ligation and Puncture-Induced Sepsis

• Published in: Molecules and cells Vol. 44; no. 12; pp. 893 - 899
• Main Authors: Park, Donghwan, Ro, MyungJa, Lee, A-Jin, Kwak, Dong-Wook, Chung, Yunro, Kim, Jae-Hong
• Format: Journal Article
• Language: English
• Published: United States Korean Society for Molecular and Cellular Biology 01.12.2021; 한국분자세포생물학회
• Subjects: Animals; Cecum - metabolism; Cecum - pathology; Cecum - surgery; Cytokines - metabolism; Disease Models, Animal; Ligation; Mice; Punctures; Receptors, Leukotriene B4 - metabolism; Sepsis - metabolism; 생물학; cytokines; leukotrienes; sepsis; BLT2; cecal ligation and puncture
• ISSN: 1016-8478; 0219-1032
• DOI: 10.14348/molcells.2021.0159

BLT2 is a low-affinity receptor for leukotriene B , 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 (LTB [leukotriene B ] and 12( )-HETE [12( )-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-LO and 12-LO, which are synthesizing enzymes for LTB and 12( )-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-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.