Daphnetin prevents methicillin-resistant Staphylococcus aureus infection by inducing autophagic response
| Autor: | Qinan Wu, Cheng Cheng, Weihong Ge, Wei Zhang, Bo Zhu, Yin Lu, Liyun Shi, Wenbin Shang, Shiqin Zhuo, Long He |
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| Rok vydání: | 2019 |
| Předmět: |
Male
Methicillin-Resistant Staphylococcus aureus 0301 basic medicine medicine.drug_class Immunology Antibiotics Anti-Inflammatory Agents Inflammation medicine.disease_cause Microbiology Mice 03 medical and health sciences 0302 clinical medicine Pneumonia Staphylococcal Autophagy medicine Animals Immunology and Allergy Macrophage Umbelliferones Pharmacology business.industry Macrophages Bacterial pneumonia Antimicrobial medicine.disease Methicillin-resistant Staphylococcus aureus Anti-Bacterial Agents Mice Inbred C57BL Pneumonia RAW 264.7 Cells 030104 developmental biology Staphylococcus aureus 030220 oncology & carcinogenesis Cytokines Female medicine.symptom business |
| Zdroj: | International Immunopharmacology. 72:195-203 |
| ISSN: | 1567-5769 |
| Popis: | The bacterial pneumonia caused by methicillin-resistant Staphylococcus aureus (MRSA) is a potentially fatal disease, featured with extensive infection, inflammation, and airway dysfunction. With the increasing emerging of drug-resistant strains, new therapeutic strategies beyond canonical antibiotic treatment are pressingly needed. Daphnetin (DAPH) is a natural coumarin derivative with anti-inflammation, anti-microorganism and anti-oxidative properties. However, the protective effect of DAPH on S. aureus-caused pneumonia and the mechanism involved are never explored. Here we show that DAPH treatment conferred substantial protection against S. aureus-induced pneumonia, characterized by the reduced inflammatory responses, the augmented bacterial clearance and the alleviated tissue damage. Our study indicates that DAPH significantly enhanced mTOR-dependent autophagic pathway, leading to the boosted microphage bactericidal activity and the suppressed inflammatory responses. Inhibition of autophagic pathway therefore largely abolished DAPH-elicited repression of inflammatory response and macrophage anti-bacterial capability. Together, we herein not only identify a novel, natural agent to combat bacterial pneumonia, but also underscore the significance of autophagic pathway in orchestrating antimicrobial and anti-inflammatory responses, which may have important implication for the treatment of the infectious diseases, particularly that caused by obstinate, antibiotic-resistant pathogens such as MRSA. |
| Databáze: | OpenAIRE |
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