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

• Published in: The Korean journal of internal medicine Vol. 32; no. 5; pp. 865 - 874
• Main Authors: Uh, Soo-Taek, Koo, So My, Kim, Yangki, Kim, Kiup, Park, Sungwoo, Jang, An Soo, Kim, Dojin, Kim, Yong Hoon, Park, Choon-Sik
• Format: Journal Article
• Language: English
• Published: Korea (South) The Korean Association of Internal Medicine 01.09.2017; 대한내과학회
• Subjects: Acetylcysteine - pharmacology; Animals; Antioxidants - pharmacology; Caspase 1 - metabolism; Cigarette Smoking - adverse effects; Disease Models, Animal; Female; Inflammasomes - drug effects; Inflammasomes - immunology; Inflammasomes - metabolism; Interleukin-1beta - metabolism; Lung - drug effects; Lung - immunology; Lung - metabolism; Macrophages - drug effects; Macrophages - immunology; Macrophages - metabolism; Mice; Mice, Inbred C57BL; NLR Family, Pyrin Domain-Containing 3 Protein - immunology; NLR Family, Pyrin Domain-Containing 3 Protein - metabolism; Original; Pancreatic Elastase; Particulate Matter; Pulmonary Emphysema - chemically induced; Pulmonary Emphysema - immunology; Pulmonary Emphysema - metabolism; Pulmonary Emphysema - prevention & control; RAW 264.7 Cells; Signal Transduction; Time Factors; Vehicle Emissions; 내과학; Pancreatic elastase; Pulmonary disease, chronic obstructive; Inf lammasomes; Emphysema; Vehicle emissions
• ISSN: 1226-3303; 2005-6648
• DOI: 10.3904/kjim.2016.033

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. RAW 264.7 cells and 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. 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, < 0.05; DEP: 350 ± 24 pg/mL vs. 281 ± 15 pg/mL, respectively, < 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. The NLRP3-inf lammasome is activated by DEPs in tissue explants from elastase-induced emphysema animal model, and this activation is inhibited by NAC.