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Deletion of NALP3 protects against hyperoxia‐induced acute lung injury
Author(s) -
Fukumot Jutaro,
Fukumoto Itsuko,
Huynh Bao,
Cox Ruan,
Parthasarathy Prasanna Tamarapu,
Ho Matthew,
Ramanathan Gurukumar Kollongod,
Venugopal Rajan Babu,
Lockey Richard F.,
Kolliputi Narasaiah
Publication year - 2012
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.26.1_supplement.lb464
Subject(s) - hyperoxia , tunel assay , lung , pathology , bronchoalveolar lavage , parenchyma , medicine , nalp3 , h&e stain , cytokine , immunohistochemistry , inflammation , immunology , inflammasome
Objectives To determine whether NALP3 deletion has the ability to ameliorate hyperoxia‐induced acute lung injury. Methods C57BL/6 mice and age‐matched NALP3 KO mice of the same genetic background were exposed to 100% oxygen. 24–72 hours after exposure to hyperoxia, mice were sacrificed to collect bronchoalveolar lavage fluid (BAL fluid) for cell counts, cytokine measurement with ELISA, and TUNEL staining on BAL fluid cells. Additionally, after 48–72 hour exposure, lung tissues were collected for H&E and TUNEL staining on lung tisue sections, and also for Western blot analysis of Ceaved Caspase‐3 expresssion in lung tissue. Results Cell count in BAL fluid showed that infiltration of macrophages and neutrophils into lung parenchyma was significantly suppressed in KO mice. The pro‐inflammatory cytokine IL‐1β, TNF‐α, MCP‐1 and MIP‐2 levels in BAL fluid are all significantly suppresed in KO mice. Semi‐quantitative histological evaluation of H&E‐stained lung tissue sections revealed that lung pathological severity score was notably less in KO mice. TUNEL staining on lung tissue sections showed that lung epithelial cell apoptosis in NALP3 KO mice was markedly suppressed when compared to WT mice. Conclusions The deletion of NALP3 gene protects against hyperoxia‐induced acute lung injury. This result suggest that inflammasome platform can be a novel target for the treatment of acute lung injury.