title: Blocking triggering receptor expressed on myeloid cells-1 attenuates lipopolysaccharide-induced acute lung injury via inhibiting NLRP3 inflammasome activation.
abstract: Acute lung injury (ALI) is associated with high mortality and uncontrolled inflammation plays a critical role in ALI. TREM-1 is an amplifier of inflammatory response, and is involved in the pathogenesis of many infectious diseases. NLRP3 inflammasome is a member of NLRs family that contributes to ALI. However, the effect of TREM-1 on NLRP3 inflammasome and ALI is still unknown. This study aimed to determine the effect of TREM-1 modulation on LPS-induced ALI and activation of the NLRP3 inflammasome. We showed that LR12, a TREM-1 antagonist peptide, significantly improved survival of mice after lethal doses of LPS. LR12 also attenuated inflammation and lung tissue damage by reducing histopathologic changes, infiltration of the macrophage and neutrophil into the lung, and production of the pro-inflammatory cytokine, and oxidative stress. LR12 decreased expression of the NLRP3, pro-caspase-1 and pro-IL-1β, and inhibited priming of the NLRP3 inflammasome by inhibiting NF-κB. LR12 also reduced the expression of NLRP3 and caspase-1 p10 protein, and secretion of the IL-1β, inhibited activation of the NLRP3 inflammasome by decreasing ROS. For the first time, these data show that TREM-1 aggravates inflammation in ALI by activating NLRP3 inflammasome, and blocking TREM-1 may be a potential therapeutic approach for ALI.
authors.affiliation: Department of Physiology, Xiangya School of Medicine, Central South University, Changsha, Hunan 410078, China.
authors.forename: Tian
authors.initials: T
authors.lastname: Liu
authors.affiliation: Department of Physiology, Xiangya School of Medicine, Central South University, Changsha, Hunan 410078, China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Zhou
authors.affiliation: Department of Physiology, Xiangya School of Medicine, Central South University, Changsha, Hunan 410078, China.
authors.forename: Ping
authors.initials: P
authors.lastname: Li
authors.affiliation: Department of Physiology, Xiangya School of Medicine, Central South University, Changsha, Hunan 410078, China.
authors.forename: Jia-Xi
authors.initials: JX
authors.lastname: Duan
authors.affiliation: Department of Physiology, Xiangya School of Medicine, Central South University, Changsha, Hunan 410078, China.
authors.forename: Yong-Ping
authors.initials: YP
authors.lastname: Liu
authors.affiliation: Department of Physiology, Xiangya School of Medicine, Central South University, Changsha, Hunan 410078, China.
authors.forename: Guo-Ying
authors.initials: GY
authors.lastname: Sun
authors.affiliation: Department of Physiology, Xiangya School of Medicine, Central South University, Changsha, Hunan 410078, China.
authors.forename: Li
authors.initials: L
authors.lastname: Wan
authors.affiliation: Department of Physiology, Xiangya School of Medicine, Central South University, Changsha, Hunan 410078, China.|Department of Anesthesiology, Affiliated Hospital of Zunyi Medical College, Zunyi, Guizhou 56300, China.
authors.forename: Liang
authors.initials: L
authors.lastname: Dong
authors.affiliation: Department of Neurology, University of Texas Medical Branch, Galveston, TX 77555, USA.
authors.forename: Xiang
authors.initials: X
authors.lastname: Fang
authors.affiliation: State Key Laboratory of Trauma, Burns, and Combined Injury, Research Institute of Surgery, Daping Hospital, Third Military Medical University, Chongqing, 400042, China.
authors.forename: Jian-Xin
authors.initials: JX
authors.lastname: Jiang
authors.affiliation: Department of Physiology, Xiangya School of Medicine, Central South University, Changsha, Hunan 410078, China.
authors.forename: Cha-Xiang
authors.initials: CX
authors.lastname: Guan
mesh_terms: D055371:Acute Lung Injury / Q000139:chemically induced / Q000378:metabolism*; D000818:Animals; D001992:Bronchoalveolar Lavage Fluid; D016207:Cytokines / Q000378:metabolism; D058847:Inflammasomes / Q000378:metabolism*; D007249:Inflammation; D016753:Interleukin-10 / Q000378:metabolism; D053583:Interleukin-1beta / Q000378:metabolism; D008070:Lipopolysaccharides; D008168:Lung / Q000378:metabolism; D008264:Macrophages / Q000378:metabolism; D008315:Malondialdehyde / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D022423:Myeloid Cells / Q000166:cytology*; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein / Q000378:metabolism*; D009504:Neutrophils / Q000378:metabolism; D018384:Oxidative Stress; D009195:Peroxidase / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D013482:Superoxide Dismutase / Q000378:metabolism; D000073871:Triggering Receptor Expressed on Myeloid Cells-1 / Q000037:antagonists & inhibitors* / Q000378:metabolism*
chemical_list: D016207:Cytokines; C556062:IL10 protein, mouse; C587672:IL1B protein, mouse; D058847:Inflammasomes; D053583:Interleukin-1beta; D008070:Lipopolysaccharides; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; C492716:Nlrp3 protein, mouse; D017382:Reactive Oxygen Species; C517262:TREM1 protein, mouse; D000073871:Triggering Receptor Expressed on Myeloid Cells-1; D016753:Interleukin-10; D008315:Malondialdehyde; D009195:Peroxidase; D013482:Superoxide Dismutase