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The activation of NLRP3-inflammsome by stimulation of diesel exhaust particles in lung tissues from emphysema model and RAW 264.7 cell line

  • Uh, Soo-Taek (Division of Allergy and Respiratory Medicine, Soon Chun Hyang University Seoul Hospital) ;
  • Koo, So My (Division of Allergy and Respiratory Medicine, Soon Chun Hyang University Seoul Hospital) ;
  • Kim, Yangki (Division of Allergy and Respiratory Medicine, Soon Chun Hyang University Seoul Hospital) ;
  • Kim, Kiup (Division of Allergy and Respiratory Medicine, Soon Chun Hyang University Seoul Hospital) ;
  • Park, Sungwoo (Genome Research Center and Division of Allergy and Respiratory Medicine, Soon Chun Hyang University Bucheon Hospital) ;
  • Jang, An Soo (Genome Research Center and Division of Allergy and Respiratory Medicine, Soon Chun Hyang University Bucheon Hospital) ;
  • Kim, Dojin (Genome Research Center and Division of Allergy and Respiratory Medicine, Soon Chun Hyang University Bucheon Hospital) ;
  • Kim, Yong Hoon (Division of Respiratory Medicine, Soon Chun Hyang University Cheonan Hospital) ;
  • Park, Choon-Sik (Genome Research Center and Division of Allergy and Respiratory Medicine, Soon Chun Hyang University Bucheon Hospital)
  • Received : 2016.01.29
  • Accepted : 2016.10.06
  • Published : 2017.09.01

Abstract

Background/Aims: Diesel exhaust particles (DEPs) lead to elevation of reactive oxygen species, which can activate the nucleotide-binding oligomerization domain-like receptor (NLR) family members containing the pyrin domain 3 (NLRP3)-inflammasome. In this study, we elucidated whether NLRP3-inflammasome is activated by DEPs and whether antioxidants (N-acetylcysteine [NAC]) could inhibit such activation. Methods: RAW 264.7 cells and ex vivo lung tissues explants obtained from elastase-induced emphysema animal models were stimulated with cigarette smoking extract (CSE), DEPs, and lipopolysaccharide, and levels of $interleukin-1{\beta}$ ($IL-1{\beta}$), caspase-1 and nucleotide-binding oligomerization domain-like receptor (NLR) family members containing the pyrin domain (NLRP3)-inflammasome were assessed by Western blotting and immunohistochemistry. Results: NAC and caspase-1 inhibitor suppressed CSE- and DEP-induced secretion of $IL-1{\beta}$ in RAW 264.7 cells. The expression levels of the NLRP3-inflammasome and caspase-1 were upregulated in RAW 264.7 cells by stimulation with CSE and DEPs and were inhibited by NAC. CSE and DEPs increased the secretion of $IL-1{\beta}$ in lung tissues from both the normal and elastase-induced emphysema groups. The secretion of $IL-1{\beta}$ by CSE and DEPs was increased in the elastin-induced emphysema group more than that in the normal group (CSE: $309{\pm}19pg/mL$ vs. $151{\pm}13pg/mL$, respectively, p < 0.05; DEP: $350{\pm}24pg/mL$ vs. $281{\pm}15pg/mL$, respectively, p < 0.05). NAC inhibited CSE- and DEP-induced $IL-1{\beta}$ secretion in both the normal and elastase-induced emphysema groups. NLRP3-inflammasome expression as determined by immunohistochemistry was increased by CSE and DEPs in both the normal and elastin-induced emphysema groups, and was suppressed by NAC. Conclusions: The NLRP3-inflammasome is activated by DEPs in ex vivo tissue explants from elastase-induced emphysema animal model, and this activation is inhibited by NAC.

Keywords

Acknowledgement

Supported by : National Research Foundation of Korea

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