Loss of interleukin-6 enhances the inflammatory response associated with hyperoxia-induced lung injury in neonatal mice.

In bronchopulmonary dysplasia (BPD), decreased angiogenesis and alveolarization is associated with pulmonary cell death and inflammation. It is commonly observed in premature infants who required mechanical ventilation and oxygen therapy. Since enhanced interleukin-6 (IL-6) expression has been reported in infants with BPD, it was hypothesized that a decrease in IL-6 may enhance lung inflammation and decrease hyperoxia-induced neonatal lung injury in mice. In the current study, newborn wild-type (WT) and IL-6 null mice were treated with 85% O2 (hyperoxia) or 21% O2 (normoxia) for 96 h. Although the increased volume and decreased quantity of alveoli was triggered by hyperoxia in WT and IL-6 null mice, transcription and translation of proinflammatory cytokines (monocyte chemoattractant protein-1, IL-10, IL-12 and tumor necrosis factor-α) and pulmonary cell death (caspase stimulation and terminal deoxynucleotidyl-transferase-mediated dUTP nick end labeling staining) were significantly enhanced in IL-6 null mice compared with WT mice. These results suggest that the crosstalk between inflammation and cell death may be involved in hyperoxia-induced lung injury in BPD. Future treatment approaches for bronchopulmonary dysplasia should be based on the suppression of cytokine expression.

Identification of differentially expressed genes associated with asthma in children based on the bioanalysis of the regulatory network.

Asthma, the most common chronic respiratory tract disease in children, is characterized by allergy, recurring airway obstruction and bronchospasm. The aim of the present study was to screen critical differentially expressed genes (DEGs) involved in asthma in children. Gene expression in different tissues was compared between asthmatic children and healthy control subjects in order to identify DEGs associated with asthma. Protein­protein interaction (PPI) networks were constructed for the DEGs and weighted gene co­expression network analysis methods were used to further determine the functional modules associated with DEGs in different tissue samples. In addition, the gene co­expression network was constructed. Gene Ontology function analysis and pathway analysis were conducted to identify critical DEGs. The results identified numerous DEGs from the different tissue samples, including 1,662 DEGs from nasal­epithelium tissue samples, 572 DEGs from peripheral blood (PB) samples and 146 DEGs from PB mononuclear cells samples. In the PPI network, F­box only protein 6 (FBXO6), histone deacetylase 1 (HDAC1) and amyloid ß precursor protein (APP) were hub genes and served an important role in the process of asthma. In addition, proliferating cell nuclear antigen (PCNA), integrin α­4 (ITGA4), catenin α­1 (CTNNA1), nuclear factor­κB1 (NF­κB1) and mechanistic target of rapamycin (MTOR) may be critical DEGs involved in the progression of asthma in children. These results suggested that FBXO6, HDAC1 and APP may interact with PCNA, ITGA4, CTNNA1, NF­κB1 and mTOR in the progression of asthma in children.