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Deprecated: Implicit conversion from float 263.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Small 2015 ; 11 (17): 2087-97 Nephropedia Template TP
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NADPH Oxidase Dependent NLRP3 Inflammasome Activation Plays an Important Role in Lung Fibrosis by Multi-Walled Carbon Nanotubes #MMPMID25581126
Sun B; Wang X; Ji Z; Wang M; Liao YP; Chang CH; Li R; Zhang H; Nel AE; Xia T
Small 2015[May]; 11 (17): 2087-97 PMID25581126show ga
The purpose of this communication is to elucidate the key role of NADPH oxidase in NLRP3 inflammasome activation and generation of pulmonary fibrosis by multi-walled carbon nanotubes (MWCNTs). Although it is known that oxidative stress plays a role in pulmonary fibrosis by single-walled CNTs, the role of specific sources of reactive oxygen species (ROS), including NADPH oxidase, in inflammasome activation remains to be clarified. In this study, three long aspect ratio (LAR) materials (MWCNTs, SWCNTs, and silver nanowires) are used to compare with spherical carbon black and silver nanoparticles for their ability to trigger oxygen burst activity and NLRP3 assembly. All LAR materials but not spherical nanoparticles induce robust NADPH oxidase activation and respiratory burst activity in THP-1 cells, which are blunted in p22phox deficient cells. NADPH oxidase is directly involved in lysosome damage by LAR materials, as demonstrated by decreased cathepsin B release and IL-1? production in p22phox deficient cells. Reduced respiratory burst activity and inflammasome activation are also observed in bone marrow-derived macrophages from p47phox deficient mice. Moreover, p47phox deficient mice have reduced IL-1? production and lung collagen deposition in response to MWCNTs. Lung fibrosis is also suppressed by N-acetyl-cysteine (NAC) in wild type animals exposed to MWCNTs.