Background: It was demonstrated that membrane-associated RING-CH 1 (March 1) might play an important role in the pathogenesis of asthma. Methods: The levels of mRNA and protein were measured by qRT-PCR and Western blot, respectively. Immunofluorescence assay was used to determine whether March1 co-locates with HDAC11. Co-immunoprecipitation was performed to examine the combination of proteins. Moreover, luciferase assay was used to measure the promoter activity of genes. Results: The mRNA and protein levels of both March1 and OX40 ligand (OX40L) were increased in the dendritic cells (DCs) from asthmatic children and asthmatic animals. Histone deacetylase 11 (HDAC11) protein was decreased in the DCs from asthmatic children and asthmatic model. Increasing of March1 or decreasing of March1 only affect the expression of HDAC11 in protein level. Besides, increasing of HDAC11 could inhibit OX40L expression, and decreasing of HDAC11 promoted OX40L expression in house dust mites (HDMs)-treated DCs. Increasing of HDAC11 notably reversed the promotion of March1 to OX40L expression. Our data further proved that March1 reduced the protein level of HDAC11 through inducing ubiquitination and degradation. HDAC11 combined with krüppel-like factor 4 (KLF4) to decrease the activity of OX40L gene promoter, thus to downregulate the level of OX40L. Conclusion: Overall, our data showed that HDAC11 promoted KLF4-dependent OX40L decreasing. However, March1 promoted OX40L expression through enhancing the ubiquitination and degradation of HDAC11 and subsequent blocking the inhibition of HDAC11 to OX40L.
ObjectiveClimate and environmental change is a well-known factor causing bronchial asthma in children. After the outbreak of coronavirus disease (COVID-19), climate and environmental changes have occurred. The present study investigated the relationship between climate changes (meteorological and environmental factors) and the number of hospitalizations for pediatric bronchial asthma in Suzhou before and after the COVID-19 pandemic.MethodsFrom 2017 to 2021, data on daily inpatients diagnosed with bronchial asthma at Children's Hospital of Soochow University were collected. Suzhou Meteorological and Environmental Protection Bureau provided daily meteorological and environmental data. To assess the relationship between bronchial asthma-related hospitalizations and meteorological and environmental factors, partial correlation and multiple stepwise regression analyses were used. To estimate the effects of meteorological and environmental variables on the development of bronchial asthma in children, the autoregressive integrated moving average (ARIMA) model was used.ResultsAfter the COVID-19 outbreak, both the rate of acute exacerbation of bronchial asthma and the infection rate of pathogenic respiratory syncytial virus decreased, whereas the proportion of school-aged children and the infection rate of human rhinovirus increased. After the pandemic, the incidence of an acute asthma attack was negatively correlated with monthly mean temperature and positively correlated with PM2.5. Stepwise regression analysis showed that monthly mean temperature and O3 were independent covariates (risk factors) for the rate of acute asthma exacerbations. The ARIMA (1, 0, 0) (0, 0, 0) 12 model can be used to predict temperature changes associated with bronchial asthma.ConclusionMeteorological and environmental factors are related to bronchial asthma development in children. The influence of meteorological and environmental factors on bronchial asthma may be helpful in predicting the incidence and attack rates.
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