Neonatal Streptococcus Pneumoniae pneumonia induces airway SMMHC expression through HMGB1/TLR4/ERK
| Autor: | Ziyao Guo, Guangli Zhang, Xiaoyin Tian, Zhengxiu Luo, Yuanyuan Li, Qinyuan Li |
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| Rok vydání: | 2021 |
| Předmět: |
MAPK/ERK pathway
Immunology HMGB1 Mice Myosin Respiratory Hypersensitivity medicine Animals Immunology and Allergy HMGB1 Protein Lung Mice Inbred BALB C biology medicine.diagnostic_test business.industry Smooth Muscle Myosins Pneumonia Pneumococcal respiratory system medicine.disease respiratory tract diseases Toll-Like Receptor 4 Pneumonia Streptococcus pneumoniae Bronchoalveolar lavage Animals Newborn Gene Expression Regulation biology.protein TLR4 Phosphorylation Airway business Signal Transduction |
| Zdroj: | Immunology Letters. 240:149-158 |
| ISSN: | 0165-2478 |
| DOI: | 10.1016/j.imlet.2021.10.005 |
| Popis: | Background Our previous study showed that neonatal S. pneumoniae pneumonia promoted airway smooth muscle myosin heavy chain (SMMHC) expression and AHR development. Researches demonstrated HMGB1, TLR4 and ERK are involved in smooth muscle contractile protein expression, so we hypothesis that HMGB1/TLR4/ERK pathway participated in airway SMMHC overexpression in neonatal S. pneumoniae pneumonia model. Method Neonatal (1-week-old) BALB/c mice were intranasal inoculated with D39 to establish non-lethal S. pneumoniae pneumonia model. TLR4 was inhibited 2 weeks after infection with TLR4 specific inhibitor (TAK-242). Five weeks after infection, the bronchoalveolar lavage fluid (BALF) and lungs of neonatal S. pneumoniae pneumonia and mock infection mice with or without TLR4 inhibition were collected to assess the expressions of HMGB1, TLR4 and p-ERK1/2. Airway Hyperresponsiveness (AHR) of the three groups was determined by whole-body plethysmograph. Results Our results demonstrated that neonatal S. pneumoniae pneumonia promoted HMGB1/TLR4 production, SMMHC expression and AHR development significantly, with ERK1/2 phosphorylation decreased remarkably. TLR4 inhibition after pneumonia significantly increased ERK1/2 phosphorylation, reversed airway SMMHC overexpression and alleviated AHR. Conclusion Neonatal S. pneumoniae pneumonia promotes airway SMMHC expression and AHR through HMGB1/TLR4/ERK. |
| Databáze: | OpenAIRE |
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