The activation of NLRP3-inflammsome by stimulation of diesel exhaust particles in lung tissues from emphysema model and RAW 264.7 cell line
- 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 nelastase- 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 +/- 19 pg/mL vs. 151 +/- 13 pg/mL, respectively, p < 0.05; DEP: 350 +/- 24 pg/mL vs. 281 +/- 15 pg/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.
- All Author(s)
- S. T. Uh
; S. M. Koo
; Y. Kim
; K. Kim
; S. Park
; A. S. Jang
; D. Kim
; Y. H. Kim
; C. S. Park
- Issued Date
- 2017
- Type
- Article
- Keyword
- Pulmonary disease; chronic obstructive; Emphysema; Inf lammasomes; Vehicle emissions; Pancreatic elastase
- Publisher
- 대한내과학회
- ISSN
- 1226-3303
- Citation Title
- Korean Journal of Internal Medicine
- Citation Volume
- 32
- Citation Number
- 5
- Citation Start Page
- 865
- Citation End Page
- 874
- Language(ISO)
- eng
- DOI
- 10.3904/kjim.2016.033
- URI
- http://schca-ir.schmc.ac.kr/handle/2022.oak/640
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