Inhibition of NLRP9b attenuates acute lung injury through suppressing inflammation, apoptosis and oxidative stress in murine and cell models
- Department of Pediatric, Baoji Maternal and Child Health Hospital, Baoji City 721000, Shaanxi (China)
- Department of Pediatric, The Second Affiliated Hospital, Shaanxi University of Traditional Chinese Medicine, Shanxi 712000 (China)
- Department of Child Healthcare, Northwest Women and Children Hospital, Xi'an, Shaanxi 710061 (China)
- Department of Pediatric, Xi'an NO.3 Hospital, Xi'an, Shaanxi 710018 (China)
Highlights: • NLRP9b-deficiency suppresses inflammation and apoptosis in CLP-induced ALI in mice. • NLRP9b-knockout reduces the generation of pro-inflammatory cytokines in ALI mice. • Inhibition of NLRP9b suppresses inflammation and apoptosis by reducing ROS generation in LPS-stimulated MLE-12 cells. Acute lung injury (ALI), known a severe disease along with high morbidity and mortality, is lacking of specific therapies. Inflammation, apoptosis and oxidative stress are critical pathologies that contribute to ALI. Recently, there is study indicated that NLRP9b, a NOD-like receptor (NLR) member, is critical in modulation of inflammatory response. However, the effects of NLRP9b on sepsis-associated ALI, and the underlying molecular mechanism have not been understood. In the present study, the wild type (WT) and NLRP9b-knockout (NLRP9b{sup −/-}) mice with C57B/L6 background were subjected to a cecal ligation and puncture (CLP) for ALI murine model establishment. The findings indicated that NLRP9b{sup −/-} improved the survival rate of CLP-induced ALI mice, and inhibited pulmonary histopathological alterations, inflammation, and apoptosis. NLRP9b{sup −/-} reduced the activation of inhibitor of κBα/nuclear factor kappa B (IκBα/NF-κB), apoptosis-associated speck-like protein containing a Caspase-recruitment domain (ASC)/Casapse-1 and Caspase-3/poly (ADP-ribose) polymerase (PARP) signaling pathways in CLP-challenged mice with ALI. In vitro, mouse epithelial cells (MLE-12) were incubated with lipopolysaccharide (LPS) or recombinant NLRP9b caused a significant increased of pro-inflammatory cytokines or chemokine, and reactive oxygen species (ROS) generation; however, these changes were markedly alleviated by NLRP9-knockdown using its specific siRNA sequence. Pre-treatment of MLE-12 cells with ROS scavenger of N-acetylcysteine (NAC) remarkably decreased lipopolysaccharide (LPS)- and rMuNLRP9-induced production of ROS, and the secretion of inflammatory cytokines or chemokine, as well as the activity of IκBα/NF-κB, ASC/Casapse-1 and Caspase-3/PARP signaling pathways. Together, the findings here suggested that NLRP9b played an essential role in lung inflammation, apoptosis and oxidative stress of sepsis-induced ALI animal model or in LPS-induced MLE-12 cells, providing that NLRP9b inhibition might be a potential therapeutic option for ALI.
- OSTI ID:
- 23105631
- Journal Information:
- Biochemical and Biophysical Research Communications, Vol. 503, Issue 2; Other Information: Copyright (c) 2018 Published by Elsevier Inc.; Country of input: International Atomic Energy Agency (IAEA); ISSN 0006-291X
- Country of Publication:
- United States
- Language:
- English
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