摘要
Exposure to airborne particulate matter (PM)not only causes lung inflammation and chronic respiratory diseases, but also increases the incidence and mortality of cardiopulmonary diseases. The nucleotide-binding domain and leucine-rich repeat protein 3 (NLRP3)inflammasome activation has been shown to play a critical role in the formation of many chronic disorders. On the other hand, carbon monoxide (CO)has been shown to possess anti-inflammatory and antioxidant effects in many tissues and organs. Here, we investigated the effects and mechanisms of carbon monoxide releasing molecule-2 (CORM-2)on PM-induced inflammatory responses in human pulmonary alveolar epithelial cells (HPAEpiCs). We found that PM induced C-reactive protein (CRP)expression, NLRP3 inflammasome activation, IL-1β secretion, and caspase-1 activation, which were inhibited by pretreatment with CORM-2. In addition, transfection with siRNA of Toll-like receptor 2 (TLR2)or TLR4 and pretreatment with an antioxidant (N-acetyl-cysteine, NAC), the inhibitor of NADPH oxidase (diphenyleneiodonium, DPI), or a mitochondria-specific superoxide scavenger (MitoTEMPO)reduced PM-induced inflammatory responses. CORM-2 also inhibited PM-induced NADPH oxidase activity and NADPH oxidase- and mitochondria-derived ROS generation. However, pretreatment with inactivate CORM-2 (iCORM-2)had no effects on PM-induced inflammatory responses. Finally, we showed that CORM-2 inhibited PM-induced CRP, NLRP3 inflammasome, and ASC protein expression in the lung tissues of mice and IL-1β levels in the serum of mice. PM-enhanced leukocyte count in bronchoalveolar lavage fluid in mice was reduced by CORM-2. The results of this study suggested a protective role of CORM-2 in PM-induced lung inflammation by inhibiting the TLR2 and TLR4/ROS-NLRP3 inflammasome-CRP axial.
| 原文 | 英語 |
|---|---|
| 頁（從 - 到） | 163-174 |
| 頁數 | 12 |
| 期刊 | Molecular Immunology |
| 卷 | 112 |
| DOIs | |
| 出版狀態 | 已發佈 - 八月 1 2019 |
指紋
ASJC Scopus subject areas
- Immunology
- Molecular Biology
引用此文
Carbon monoxide releasing molecule-2 protects against particulate matter-induced lung inflammation by inhibiting TLR2 and 4/ROS/NLRP3 inflammasome activation. / Lee, Chiang Wen; Chi, Miao Ching; Hsu, Lee Fen; Yang, Chuen Mao; Hsu, Tsui Hua; Chuang, Chu Chun; Lin, Wei Ning; Chu, Pei Ming; Lee, I. Ta.
於: Molecular Immunology, 卷 112, 01.08.2019, p. 163-174.研究成果: 雜誌貢獻 › 文章
}
TY - JOUR
T1 - Carbon monoxide releasing molecule-2 protects against particulate matter-induced lung inflammation by inhibiting TLR2 and 4/ROS/NLRP3 inflammasome activation
AU - Lee, Chiang Wen
AU - Chi, Miao Ching
AU - Hsu, Lee Fen
AU - Yang, Chuen Mao
AU - Hsu, Tsui Hua
AU - Chuang, Chu Chun
AU - Lin, Wei Ning
AU - Chu, Pei Ming
AU - Lee, I. Ta
PY - 2019/8/1
Y1 - 2019/8/1
N2 - Exposure to airborne particulate matter (PM)not only causes lung inflammation and chronic respiratory diseases, but also increases the incidence and mortality of cardiopulmonary diseases. The nucleotide-binding domain and leucine-rich repeat protein 3 (NLRP3)inflammasome activation has been shown to play a critical role in the formation of many chronic disorders. On the other hand, carbon monoxide (CO)has been shown to possess anti-inflammatory and antioxidant effects in many tissues and organs. Here, we investigated the effects and mechanisms of carbon monoxide releasing molecule-2 (CORM-2)on PM-induced inflammatory responses in human pulmonary alveolar epithelial cells (HPAEpiCs). We found that PM induced C-reactive protein (CRP)expression, NLRP3 inflammasome activation, IL-1β secretion, and caspase-1 activation, which were inhibited by pretreatment with CORM-2. In addition, transfection with siRNA of Toll-like receptor 2 (TLR2)or TLR4 and pretreatment with an antioxidant (N-acetyl-cysteine, NAC), the inhibitor of NADPH oxidase (diphenyleneiodonium, DPI), or a mitochondria-specific superoxide scavenger (MitoTEMPO)reduced PM-induced inflammatory responses. CORM-2 also inhibited PM-induced NADPH oxidase activity and NADPH oxidase- and mitochondria-derived ROS generation. However, pretreatment with inactivate CORM-2 (iCORM-2)had no effects on PM-induced inflammatory responses. Finally, we showed that CORM-2 inhibited PM-induced CRP, NLRP3 inflammasome, and ASC protein expression in the lung tissues of mice and IL-1β levels in the serum of mice. PM-enhanced leukocyte count in bronchoalveolar lavage fluid in mice was reduced by CORM-2. The results of this study suggested a protective role of CORM-2 in PM-induced lung inflammation by inhibiting the TLR2 and TLR4/ROS-NLRP3 inflammasome-CRP axial.
AB - Exposure to airborne particulate matter (PM)not only causes lung inflammation and chronic respiratory diseases, but also increases the incidence and mortality of cardiopulmonary diseases. The nucleotide-binding domain and leucine-rich repeat protein 3 (NLRP3)inflammasome activation has been shown to play a critical role in the formation of many chronic disorders. On the other hand, carbon monoxide (CO)has been shown to possess anti-inflammatory and antioxidant effects in many tissues and organs. Here, we investigated the effects and mechanisms of carbon monoxide releasing molecule-2 (CORM-2)on PM-induced inflammatory responses in human pulmonary alveolar epithelial cells (HPAEpiCs). We found that PM induced C-reactive protein (CRP)expression, NLRP3 inflammasome activation, IL-1β secretion, and caspase-1 activation, which were inhibited by pretreatment with CORM-2. In addition, transfection with siRNA of Toll-like receptor 2 (TLR2)or TLR4 and pretreatment with an antioxidant (N-acetyl-cysteine, NAC), the inhibitor of NADPH oxidase (diphenyleneiodonium, DPI), or a mitochondria-specific superoxide scavenger (MitoTEMPO)reduced PM-induced inflammatory responses. CORM-2 also inhibited PM-induced NADPH oxidase activity and NADPH oxidase- and mitochondria-derived ROS generation. However, pretreatment with inactivate CORM-2 (iCORM-2)had no effects on PM-induced inflammatory responses. Finally, we showed that CORM-2 inhibited PM-induced CRP, NLRP3 inflammasome, and ASC protein expression in the lung tissues of mice and IL-1β levels in the serum of mice. PM-enhanced leukocyte count in bronchoalveolar lavage fluid in mice was reduced by CORM-2. The results of this study suggested a protective role of CORM-2 in PM-induced lung inflammation by inhibiting the TLR2 and TLR4/ROS-NLRP3 inflammasome-CRP axial.
KW - Carbon monoxide
KW - Inflammasome
KW - Lung inflammation
KW - Particulate matter
KW - Reactive oxygen species
UR - http://www.scopus.com/inward/record.url?scp=85067988593&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85067988593&partnerID=8YFLogxK
U2 - 10.1016/j.molimm.2019.05.005
DO - 10.1016/j.molimm.2019.05.005
M3 - Article
C2 - 31153046
AN - SCOPUS:85067988593
VL - 112
SP - 163
EP - 174
JO - Molecular Immunology
JF - Molecular Immunology
SN - 0161-5890
ER -