Background:Silica nanoparticles(SiNPs),commonly utilized in industrial and biomedical fields,are known to provoke pulmonary inflammation by elevating cyclooxygenase-2(COX-2)levels in human pulmonary alveolar epithelia...Background:Silica nanoparticles(SiNPs),commonly utilized in industrial and biomedical fields,are known to provoke pulmonary inflammation by elevating cyclooxygenase-2(COX-2)levels in human pulmonary alveolar epithelial cells(HPAEpiCs).Salvianolic acid A(SAA),a water-soluble polyphenol extracted from Salvia miltiorrhiza(Danshen),possesses well-documented antioxidant and anti-inflammatory activities.Nevertheless,its potential to counteract SiNP-induced inflammatory responses in the lung has not been thoroughly explored.Objective:This study aimed to evaluate the protective role and mechanistic actions of SAA against SiNP-triggered inflammation in both cellular and animal models.Methods:HPAEpiCs were pre-incubated with SAA prior to SiNP exposure to investigate changes in COX-2 expression and prostaglandin E2(PGE2)secretion.A murine model of SiNP-induced lung inflammation was used for in vivo validation.Key inflammatory signaling proteins,including c-Src,PKCα,p42/p44MAPK,and NF-κB p65,were analyzed for phosphorylation status.NF-κB promoter activity was also assessed.Pharmacological inhibitors and siRNA-mediated silencing were employed to verify the signaling cascade responsible for COX-2 regulation.Results:SAA treatment markedly suppressed SiNP-induced upregulation of COX-2 and PGE2 in bothHPAEpiCs andmouse lung tissues.SAA also reduced the activation(phosphorylation)of c-Src,PKCα,p42/p44 MAPK,and NF-κB p65,alongside diminishing NF-κB transcriptional activity.Functional studies using inhibitors and gene silencing further supported the involvement of these pathways inmediating the observed anti-inflammatory effect.Conclusion:By concurrently targeting several upstream pro-inflammatory signaling pathways,SAA demonstrates robust potential in alleviating SiNP-induced lung inflammation.These results highlight SAA as a promising candidate for therapeutic intervention in environmentally triggered respiratory conditions.展开更多
基金supported by the National Science and Technology Council,Taiwan[Grant number:NSTC111-2320-B-030-013]as well as the Chang Gung University of Science Foundation,Taiwan[Grant number:ZRRPF6N0011].
文摘Background:Silica nanoparticles(SiNPs),commonly utilized in industrial and biomedical fields,are known to provoke pulmonary inflammation by elevating cyclooxygenase-2(COX-2)levels in human pulmonary alveolar epithelial cells(HPAEpiCs).Salvianolic acid A(SAA),a water-soluble polyphenol extracted from Salvia miltiorrhiza(Danshen),possesses well-documented antioxidant and anti-inflammatory activities.Nevertheless,its potential to counteract SiNP-induced inflammatory responses in the lung has not been thoroughly explored.Objective:This study aimed to evaluate the protective role and mechanistic actions of SAA against SiNP-triggered inflammation in both cellular and animal models.Methods:HPAEpiCs were pre-incubated with SAA prior to SiNP exposure to investigate changes in COX-2 expression and prostaglandin E2(PGE2)secretion.A murine model of SiNP-induced lung inflammation was used for in vivo validation.Key inflammatory signaling proteins,including c-Src,PKCα,p42/p44MAPK,and NF-κB p65,were analyzed for phosphorylation status.NF-κB promoter activity was also assessed.Pharmacological inhibitors and siRNA-mediated silencing were employed to verify the signaling cascade responsible for COX-2 regulation.Results:SAA treatment markedly suppressed SiNP-induced upregulation of COX-2 and PGE2 in bothHPAEpiCs andmouse lung tissues.SAA also reduced the activation(phosphorylation)of c-Src,PKCα,p42/p44 MAPK,and NF-κB p65,alongside diminishing NF-κB transcriptional activity.Functional studies using inhibitors and gene silencing further supported the involvement of these pathways inmediating the observed anti-inflammatory effect.Conclusion:By concurrently targeting several upstream pro-inflammatory signaling pathways,SAA demonstrates robust potential in alleviating SiNP-induced lung inflammation.These results highlight SAA as a promising candidate for therapeutic intervention in environmentally triggered respiratory conditions.
