RESUMO
PURPOSE: To investigate the efficacy and mechanisms of root tuber of Polygonum ciliinerve (Nakai) ohwi (rPC) which has been used to treat bacterial infection in traditional Chinese medicine. METHODS: With the mouse model of Staphylococcus aureus (S. aureus) pneumonia, the phenotype of rPC treated mice, including body weight, mortality, lung slices and bacterial burden were evaluated. Furthermore, inflammatory factors in bronchoalveolar lavage (BAL) were determined by ELISA and the distribution of T cells in lung was assessed by immunofluorescence assay. RESULTS: rPC treatment could dose-dependently reduce weight loss and mortality in S. aureus-infected mice. Upon 10 mg/ml rPC treatment, S. aureus-infected mice showed about 8 grams increase in body weight (P<0.001) and 50% enhancement in mortality. The integrity of lung tissue and bacterial burden were also improved by rPC treatment. Moreover, rPC was found to modulate the immune response in infection. CONCLUSION: rPC has therapeutic potential for S. aureus infections and pneumonia with immunomodulatory functions.
Assuntos
Antibacterianos/farmacologia , Medicamentos de Ervas Chinesas/farmacologia , Imunomodulação/efeitos dos fármacos , Pneumonia Estafilocócica/prevenção & controle , Polygonum/química , Substâncias Protetoras/farmacologia , Staphylococcus aureus/efeitos dos fármacos , Animais , Líquido da Lavagem Broncoalveolar/química , Quimiocina CCL2/análise , Contagem de Colônia Microbiana , Ensaio de Imunoadsorção Enzimática , Imuno-Histoquímica , Interleucina-6/análise , Pulmão/efeitos dos fármacos , Pulmão/patologia , Camundongos Endogâmicos C57BL , Pneumonia Estafilocócica/tratamento farmacológico , Pneumonia Estafilocócica/patologia , Reprodutibilidade dos Testes , Fatores de Tempo , Resultado do Tratamento , Fator de Necrose Tumoral alfa/análiseRESUMO
Abstract Purpose: To investigate the efficacy and mechanisms of root tuber of Polygonum ciliinerve (Nakai) ohwi (rPC) which has been used to treat bacterial infection in traditional Chinese medicine. Methods: With the mouse model of Staphylococcus aureus (S. aureus) pneumonia, the phenotype of rPC treated mice, including body weight, mortality, lung slices and bacterial burden were evaluated. Furthermore, inflammatory factors in bronchoalveolar lavage (BAL) were determined by ELISA and the distribution of T cells in lung was assessed by immunofluorescence assay. Results: rPC treatment could dose-dependently reduce weight loss and mortality in S. aureus-infected mice. Upon 10 mg/ml rPC treatment, S. aureus-infected mice showed about 8 grams increase in body weight (P<0.001) and 50% enhancement in mortality. The integrity of lung tissue and bacterial burden were also improved by rPC treatment. Moreover, rPC was found to modulate the immune response in infection. Conclusion: rPC has therapeutic potential for S. aureus infections and pneumonia with immunomodulatory functions.
Assuntos
Animais , Pneumonia Estafilocócica/prevenção & controle , Staphylococcus aureus/efeitos dos fármacos , Medicamentos de Ervas Chinesas/farmacologia , Substâncias Protetoras/farmacologia , Polygonum/química , Imunomodulação/efeitos dos fármacos , Antibacterianos/farmacologia , Pneumonia Estafilocócica/patologia , Pneumonia Estafilocócica/tratamento farmacológico , Fatores de Tempo , Ensaio de Imunoadsorção Enzimática , Líquido da Lavagem Broncoalveolar/química , Imuno-Histoquímica , Contagem de Colônia Microbiana , Reprodutibilidade dos Testes , Interleucina-6/análise , Fator de Necrose Tumoral alfa/análise , Resultado do Tratamento , Quimiocina CCL2/análise , Pulmão/efeitos dos fármacos , Pulmão/patologia , Camundongos Endogâmicos C57BLRESUMO
INTRODUCTION: Curcumin has remarkable anti-inflammatory and antioxidant properties. However, its effects on bacterium-induced acute lung injury (ALI) are not fully understood. OBJECTIVE: To investigate the protective effects of curcumin on a mouse model of S. aureus-induced ALI. METHODS: Mice were pretreated with intraperitoneal injection of curcumin or vehicle 2 h before Staphylococcus aureus instillation. The survival rate and bacterial burden after infection were recorded. Mice were sacrificed for the analyses of severity of pneumonia, integrity of lung barrier, disorder of coagulation cascades and extent of inflammation 12 h postinfection. The production of proinflammatory cytokines and chemokines in the lung and bronchoalveolar lavage fluid was detected. RESULTS: Pretreatment with curcumin markedly attenuated S. aureus-induced pneumonia, barrier disruption, lung edema and vascular leakage. Activation of plasminogen activator inhibitor-1 and infiltration of neutrophils were reduced by curcumin, together with lower levels of proinflammatory cytokines and chemokines. CONCLUSION: Curcumin can alleviate S. aureus-induced ALI through multiple pathways.
Assuntos
Lesão Pulmonar Aguda/tratamento farmacológico , Lesão Pulmonar Aguda/microbiologia , Anti-Inflamatórios não Esteroides/uso terapêutico , Curcumina/uso terapêutico , Pneumonia Estafilocócica/tratamento farmacológico , Staphylococcus aureus , Lesão Pulmonar Aguda/patologia , Animais , Modelos Animais de Doenças , Feminino , Injeções Intraperitoneais , Camundongos , Camundongos Endogâmicos C57BL , Pneumonia Estafilocócica/complicações , Pneumonia Estafilocócica/patologiaRESUMO
BACKGROUND: Linezolid (LZD) is beneficial to patients with MRSA pneumonia, but whether and how LZD influences global host lung immune responses at the mRNA level during MRSA-mediated pneumonia is still unknown. METHODS: A lethal mouse model of MRSA pneumonia mediated by USA300 was employed to study the influence of LZD on survival, while the sublethal mouse model was used to examine the effect of LZD on bacterial clearance and lung gene expression during MRSA pneumonia. LZD (100mg/kg/day, IP) was given to C57Bl6 mice for three days. On Day 1 and Day 3 post infection, bronchoalveolar lavage fluid (BALF) protein concentration and levels of cytokines including IL6, TNFα, IL1ß, Interferon-γ and IL17 were measured. In the sublethal model, left lungs were used to determine bacterial clearance and right lungs for whole-genome transcriptional profiling of lung immune responses. RESULTS: LZD therapy significantly improved survival and bacterial clearance. It also significantly decreased BALF protein concentration and levels of cytokines including IL6, IL1ß, Interferon-γ and IL17. No significant gene expression changes in the mouse lungs were associated with LZD therapy. CONCLUSION: LZD is beneficial to MRSA pneumonia, but it does not modulate host lung immune responses at the transcriptional level.
Assuntos
Lesão Pulmonar Aguda/tratamento farmacológico , Antibacterianos/farmacologia , Linezolida/farmacologia , Pulmão/efeitos dos fármacos , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Pneumonia Estafilocócica/tratamento farmacológico , Lesão Pulmonar Aguda/metabolismo , Lesão Pulmonar Aguda/patologia , Animais , Proteínas de Bactérias/metabolismo , Citocinas/metabolismo , Modelos Animais de Doenças , Avaliação Pré-Clínica de Medicamentos , Expressão Gênica/efeitos dos fármacos , Perfilação da Expressão Gênica , Pulmão/metabolismo , Pulmão/patologia , Masculino , Camundongos Endogâmicos C3H , Análise em Microsséries , Pneumonia Estafilocócica/metabolismo , Pneumonia Estafilocócica/patologia , Reação em Cadeia da Polimerase em Tempo Real , Análise de SobrevidaRESUMO
In this study, hemolysis, Western blot, and real-time RT-PCR assays were performed to evaluate silibinin's activity against S. aureus α-toxin secretion. In addition, live/dead cell staining and lactate dehydrogenase activity assays were introduced to examine the influence of silibinin on α-toxin-induced cell injury in human alveolar epithelial cells. Furthermore, we tested the influence of silibinin on S. aureus pneumonia in a mouse model. We show that silibinin inhibits the expression of α-toxin in a dose-dependent manner and alleviates α-toxin-induced lung cell injury. The IC50 of silibinin that inhibits the hemolytic activity of S. aureus was 14.33 µg/mL for strain 8325-4. Moreover, this compound provides effective protection on the lung injury of staphylococcal pneumonia.