The activation of NLRP3-inflammsome by stimulation of diesel exhaust particles in lung tissues from emphysema model and RAW 264.7 cell line.
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.
['Uh|Soo-Taek|ST|', 'Koo|So My|SM|', 'Kim|Yangki|Y|', 'Kim|Kiup|K|', 'Park|Sungwoo|S|', 'Jang|An Soo|AS|', 'Kim|Dojin|D|', 'Kim|Yong Hoon|YH|', 'Park|Choon-Sik|CS|']
D000111:Acetylcysteine D000818:Animals D000975:Antioxidants D020170:Caspase 1 D000073865:Cigarette Smoking D004195:Disease Models, Animal D005260:Female D058847:Inflammasomes D053583:Interleukin-1beta D008168:Lung D008264:Macrophages D051379:Mice D008810:Mice, Inbred C57BL D000071199:NLR Family, Pyrin Domain-Containing 3 Protein D010196:Pancreatic Elastase D052638:Particulate Matter D011656:Pulmonary Emphysema D000067996:RAW 264.7 Cells D015398:Signal Transduction D013997:Time Factors D001335:Vehicle Emissions
Emphysema Inf lammasomes Pancreatic elastase Pulmonary disease, chronic obstructive Vehicle emissions