RESUMO
Cigarette smoke extract (CSE) is known as a significant contributor to chronic obstructive pulmonary disease (COPD). Propofol, an anesthetic agent, has been studied for its potential protective effects against lung damage. This study aimed to elucidate the protective mechanisms of propofol against CSE-induced damage in human bronchial epithelial 16HBE cells. In CSE-induced 16HBE cells treated by propofol with or without transfection of nuclear factor erythroid 2-related factor 2 (Nrf2) interference plasmids, CCK-8 assay and lactate dehydrogenase (LDH) assay evaluated cytotoxicity. TUNEL assay and Western blot appraised cell apoptosis. ELISA and relevant assay kits severally measured inflammatory and oxidative stress levels. DCFH-DA fluorescent probe detected intracellular reactive oxygen species (ROS) activity. Immunofluorescence staining and Western blot estimated pyroptosis. Also, Western blot analyzed the expression of Nrf2/NLR family pyrin domain containing 3 (NLRP3) signaling-related proteins. Propofol was found to enhance the viability, reduce LDH release, and alleviate the apoptosis, inflammatory response, oxidative stress and pyroptosis in CSE-induced 16HBE cells in a concentration-dependent manner. Meanwhile, propofol decreased NLRP3 expression while raised Nrf2 expression. Further, after Nrf2 was silenced, the impacts of propofol on Nrf2/NLRP3 signaling, LDH release, apoptosis, inflammatory response, oxidative stress and pyroptosis in CSE-exposed 16HBE cells were eliminated. Conclusively, propofol may exert protective effects against CSE-induced damage in 16HBE cells, partly through the modulation of the Nrf2/NLRP3 signaling pathway, suggesting a potential therapeutic role for propofol in CSE-induced bronchial epithelial cell damage.
Assuntos
Brônquios , Células Epiteliais , Fator 2 Relacionado a NF-E2 , Proteína 3 que Contém Domínio de Pirina da Família NLR , Estresse Oxidativo , Propofol , Transdução de Sinais , Humanos , Fator 2 Relacionado a NF-E2/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Propofol/farmacologia , Transdução de Sinais/efeitos dos fármacos , Células Epiteliais/metabolismo , Células Epiteliais/efeitos dos fármacos , Brônquios/metabolismo , Brônquios/efeitos dos fármacos , Brônquios/patologia , Estresse Oxidativo/efeitos dos fármacos , Linhagem Celular , Fumaça/efeitos adversos , Apoptose/efeitos dos fármacos , Piroptose/efeitos dos fármacos , Espécies Reativas de Oxigênio/metabolismo , Fumar Cigarros/efeitos adversosRESUMO
Dexmedetomidine (Dex) is a selective α2-adrenoceptor agonist and has ability to prevent inflammation and apoptosis in tissues injury. However, whether Dex could alleviate smoke-induced lung injury remains unknown. This study aimed to explore the protective effects of Dex against smoke-induced lung injury. Bronchial and alveolar epithelial cells were treated with cigarette smoke extract (CSE) for 24 h to simulate cigarette smoke-induced lung injury. Results showed that CSE reduced cell viability and increased levels of pro-inflammatory cytokines TNFα, IL-1ß and IL-6, thus activating NF-κB and COX2 expression. CSE also increased ROS generation, whereas lessened MnSOD and catalase generation. Besides, the ratio of apoptotic cells was enhanced upon CSE stimuli, together with disturbance of apoptotic-related proteins including Bcl-2, Bax and caspase-3. However, Dex reduced the damage of CSE to cell viability. The increased activities of TNFα, IL-1ß and IL-6 induced by CSE were partially attenuated by Dex. Dex also recovered the levels of NF-κB and COX2, as well as mnSOD, catalase and ROS. Furthermore, the increase of cell apoptosis together with imbalance of apoptotic proteins induced by CSE was rescued by Dex. Our results demonstrated that Dex alleviated CSE-induced lung injury through inhibition of inflammation, oxidative stress and apoptosis.
