Neonatal Streptococcus Pneumoniae pneumonia induces airway SMMHC expression through HMGB1/TLR4/ERK

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 (TAK242). 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 wholebody 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.

Automated summary

The study revealed that neonatal S. pneumoniae pneumonia promotes airway smooth muscle myosin heavy chain (SMMHC) overexpression and airway hyperresponsiveness (AHR) through the HMGB1/TLR4/ERK pathway.