CLCA1 mediates the regulatory effect of IL-13 on pediatric asthma

Abstract

ObjectiveCLCA1 is a secreted protein with protease activity, and its expression is associated with inflammatory airway diseases. This study aimed to investigate the role of CLCA1 and IL-13 in pediatric asthma.MethodsIn asthmatic and healthy children, the correlation between CLCA1 expression and blood IL-4, and IL-13 levels were investigated by serological analyses such as RT-qPCR and ELISA. The effects on the activity and apoptosis of bronchial epithelial cells following IL-13 stimulation were explored in vitro by the CCK-8 assay and flow cytometry, respectively. CLCA1 siRNA was used to knock down the expression level of bronchial epithelial cells and the effect of IL-13 stimulation on these cells was assessed by the CCK-8 assay and flow cytometry.ResultsCLCA1, IL-4, and IL-13 were highly expressed in the serum of children with asthma. CLCA1 expression was highly correlated to serum IL-13. IL-13 stimulation reduced the activity of bronchial epithelial cells in vitro and promoted apoptosis. Lastly, knockdown of CLCA1 rescued the IL-13-induced decrease in activity and apoptosis.ConclusionCLCA1 is highly expressed in children with asthma and mediates the contributory effect of IL-13 on the occurrence and development of pediatric asthma.

Comprehensive Analysis of CLCA1 Expression, Immune Infiltration and Immune Checkpoints in Colon Adenocarcinoma

“…In a mouse model of acute lung inflammation, a lack of CLCA1 resulted in leukocyte recruitment and reduced cytokine expression (Erickson et al, 2018). Macrophages were activated in vitro (Mishina et al, 2015) and are highly associated with IL-13 expression in childhood asthma (Xu et al, 2022). In ovarian cancer, the existence of intracellular chloride channels, volume regulation, and voltage-gating has been observed through experiments conducted both in vitro and in vivo.…”

“…Earlier research has shown that CLCA1 primarily participates in multiple respiratory disorders like asthma, chronic obstructive pulmonary disease (COPD), cystic fibrosis, pneumonia, and other related conditions (den Dekker et al, 2019;Higham et al, 2022). The regulation of airway mucus secretion is controlled by CLCA1 through TMEM16A (Patel et al, 2009;Centeio et al, 2021), while also facilitating the initiation and progression of asthma via its mediation of IL13 (Xu et al, 2022). Further analysis of the whole gene transcriptome of the lung showed that respiratory mucin CLCA1 and tightly connected, inflammation-related genes were differentially expressed in different asthma inflammatory phenotypes (Tan et al, 2019).…”

Editorial: Translational research in pediatric respiratory diseases: From bench to bedside

“…CLCA1 modulates mucus dynamics and homeostasis in multiple environments, such as intestinal and respiratory epithelia. In this topic, Xu et al (18) investigated associations between CLCA1 expression and IL-13 levels, which is the main biomarker of airway and blood eosinophilia, a main characteristic of type 2 asthma (19). To this end, the authors designed a full "bench-to-bedside" experimental approach.…”