The activation of NLRP3-inflammsome by stimulation of diesel exhaust particles in lung tissues from emphysema model and RAW 264.7 cell line
The Korean Journal of Internal Medicine
;
: 865-874, 2017.
Article
in English
| WPRIM
| ID: wpr-151263
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)-inf lammasome. In this study, we elucidated whether NLRP3 -inf lammasome 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-1β (IL-1β), 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-1β 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-1β in lung tissues from both the normal and elastase-induced emphysema groups. The secretion of IL-1β 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-1β 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-inf lammasome is activated by DEPs in ex vivo tissue explants from elastase-induced emphysema animal model, and this activation is inhibited by NAC.
Full text:
Available
Index:
WPRIM (Western Pacific)
Main subject:
Vehicle Emissions
/
Immunohistochemistry
/
Pancreatic Elastase
/
Smoking
/
Blotting, Western
/
Reactive Oxygen Species
/
Models, Animal
/
Pulmonary Disease, Chronic Obstructive
/
Emphysema
/
Lung
Limits:
Humans
Language:
English
Journal:
The Korean Journal of Internal Medicine
Year:
2017
Type:
Article
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