Blocking triggering receptor expressed on myeloid cells-1 attenuates lipopolysaccharide-induced acute lung injury via inhibiting NLRP3 inflammasome activation

Tian Liu, Yong Zhou, Ping Li, Jia Xi Duan, Yong Ping Liu, Guo Ying Sun, Li Wan, Liang Dong, Xiang Fang, Jian Xin Jiang, Cha Xiang Guan

Research output: Contribution to journalArticle

27 Citations (Scopus)

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-κ B. 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.

Original languageEnglish (US)
Article number39473
JournalScientific Reports
Volume6
DOIs
StatePublished - Dec 22 2016

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Inflammasomes
Acute Lung Injury
Myeloid Cells
Lipopolysaccharides
Caspase 1
Interleukin-1
Inflammation
Neutrophil Infiltration
Communicable Diseases
Pneumonia
Oxidative Stress
Macrophages
Cytokines
Lung
Peptides
Mortality
lissamine-rhodamine dodecanoic acid

ASJC Scopus subject areas

  • General

Cite this

Blocking triggering receptor expressed on myeloid cells-1 attenuates lipopolysaccharide-induced acute lung injury via inhibiting NLRP3 inflammasome activation. / Liu, Tian; Zhou, Yong; Li, Ping; Duan, Jia Xi; Liu, Yong Ping; Sun, Guo Ying; Wan, Li; Dong, Liang; Fang, Xiang; Jiang, Jian Xin; Guan, Cha Xiang.

In: Scientific Reports, Vol. 6, 39473, 22.12.2016.

Research output: Contribution to journalArticle

Liu, Tian ; Zhou, Yong ; Li, Ping ; Duan, Jia Xi ; Liu, Yong Ping ; Sun, Guo Ying ; Wan, Li ; Dong, Liang ; Fang, Xiang ; Jiang, Jian Xin ; Guan, Cha Xiang. / Blocking triggering receptor expressed on myeloid cells-1 attenuates lipopolysaccharide-induced acute lung injury via inhibiting NLRP3 inflammasome activation. In: Scientific Reports. 2016 ; Vol. 6.
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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-κ B. 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.",
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