CLCA1 exacerbates lung inflammation via p38 MAPK pathway in acute respiratory distress syndrome

Abstract

Recent research has revealed that airway epithelial calcium-activated chloride channel-1 (CLCA1) is implicated in the inflammation of multiple human respiratory diseases, but the specific role in acute respiratory distress syndrome (ARDS) remains unknown. To investigate the role of CLCA1 in ARDS, 80 participants, including 26 ARDS patients, 26 patients with community-acquired pneumonia (CAP) and 28 control subjects, were enrolled in this study. As the result shows, the level of CLCA1 was significantly increased in ARDS patients and positively correlated with neutrophil infiltration and the poor prognosis of ARDS. Then, the level of CLCA1 also elevated in the LPS-induced ARDS mouse model, and the administration of CLCA1 significantly regulated the phenotypes of ARDS in mice, such as lung injury score, BALF protein concentration, neutrophils infiltration and the secretions of inflammatory factors. Furthermore, administration of CLCA1 substantially altered the phosphorylation of p38 in the ARDS mouse model, whereas repressing the expression of CLCA1 or inhibiting the activation of p38 both alleviated the inflammatory response of ARDS. In summary, CLCA1 was notably correlated with ARDS and exacerbated the ARDS phenotypes through the p38 MAPK pathway.

Keywords:

• Acute respiratory distress syndrome
• airway epithelial cells
• airway inflammation
• CLCA1
• p38 MAPK

Authors’ contributions

Conceptualization, LS; Methodology, LZ, TZ, YC, JL, ZC, and XG; Writing-Original Draft, XL; Writing-Review & Editing, XL, WW, and LS; Funding acquisition, XL and LS. All authors contributed to the article and approved the submitted version.

Disclosure statement

No potential conflict of interest was reported by the author(s). The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Data availability statement

The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.

Additional information

Funding

This study was supported by National Natural Science Foundation of China (81570072 to LS), Key program of natural science basic research in Shaanxi Province (2022JZ-58 to LS), Discipline Boosting Program of Xijing Hospital (XJZT21CM25 to XL), Military Medicine Clinical Application Research Project of Xijing Hospital (JSYXM14 to XL).