Carbon monoxide releasing molecule-2 protects against particulate matter-induced lung inflammation by inhibiting TLR2 and 4/ROS/NLRP3 inflammasome activation
| Autor: | I-Ta Lee, Chu-Chun Chuang, Tsui-Hua Hsu, Miao-Ching Chi, Wei-Ning Lin, Chiang-Wen Lee, Lee-Fen Hsu, Pei Ming Chu, Chuen-Mao Yang |
|---|---|
| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Male Inflammasomes Immunology Interleukin-1beta Inflammation Pharmacology Protective Agents 03 medical and health sciences chemistry.chemical_compound Mice 0302 clinical medicine NLR Family Pyrin Domain-Containing 3 Protein medicine Organometallic Compounds Animals Humans Molecular Biology Cardiopulmonary disease chemistry.chemical_classification Reactive oxygen species Carbon Monoxide Mice Inbred BALB C NADPH oxidase medicine.diagnostic_test biology Superoxide Caspase 1 Inflammasome Pneumonia Toll-Like Receptor 2 Mitochondria Toll-Like Receptor 4 030104 developmental biology Bronchoalveolar lavage chemistry biology.protein TLR4 Particulate Matter medicine.symptom Reactive Oxygen Species Bronchoalveolar Lavage Fluid 030215 immunology medicine.drug Signal Transduction |
| Zdroj: | Molecular immunology. 112 |
| ISSN: | 1872-9142 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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