IL-1 signaling pathway molecules as key markers in childhood asthma.

ABSTRACT

OBJECTIVE: The prevalence of childhood asthma has been increasing in recent years. This study aims to investigate the involvement of the key molecules of IL-1 (interleukin-1) signaling pathways in pediatric patients with asthma. METHODS: Differentially expressed genes (DEGs) associated with IL-1 signaling pathways were identified with RNA-seq from peripheral blood samples collected from asthmatic or healthy children and were further verified in clinical peripheral blood samples. Cellular models and asthmatic mice were subsequently developed to validate the identified asthmatic markers. RESULTS: Among the DEGs identified by RNA-seq, eight signal transducers associated with the IL-1 signaling network, namely IL-1RN, IL-1ß, IL-1RAP, IRAK3, IL-1R1, MYD88, IRAK2, and PELI1, were found to be substantially upregulated in children with asthma. Interestingly, a significant serially increased expression of four genes (IL-1RN, IL-1RAP, IRAK3, and PELI1) was observed in healthy subjects, patients with chronic persistent asthma and patients with acute exacerbation asthma. In particular, these four genes were continuously overexpressed in recurrent patients. A significant induction of the above four genes was then observed in house dust mite (HDM)-stimulated peripheral blood mononuclear cells (PBMCs) and ovalbumin (OVA)-induced asthmatic mice. In addition, a time-dependent induction of IL-1RAP and PELI1 was also detected in HDM-treated THP-1 cells, an acute monocytic leukemia cell line. CONCLUSIONS: These results demonstrate that IL-1RN, IL-1RAP, IRAK3, and PELI1, which are signal transducers of the IL-1 signaling pathway, could serve as biomarkers for the pathogenesis of childhood asthma and for potential therapeutic targets of asthma.