Central European Journal of Immunology
eISSN: 1644-4124
ISSN: 1426-3912
Central European Journal of Immunology
Current issue Archive Manuscripts accepted About the journal Special Issues Editorial board Abstracting and indexing Subscription Contact Instructions for authors Publication charge
Editorial System
Submit your Manuscript
SCImago Journal & Country Rank
Search
Share:
Send email
Share:
abstract:
Original paper

Neutrophil elastase promotes mucin secretion in airway epithelial cells through the MARCKS/ACK1/cortactin pathway

Mingxin He
1
,
Qi Li
2
,
SHUYUAN OUYANG
1
,
Yan Liu
3
,
Juliy M. Perelman
4
,
Victor P. Kolosov
4
,
Xiangdong Zhou
2
,
Yanyan Li
1

  1. Department of Intensive Care Unit, Peking University Shenzhen Hospital, China
  2. Department of Respiratory Medicine, The First Affiliated Hospital, Hainan Medical University, China
  3. Department of Neurology, Shenzhen Hospital (Futian) of Guangzhou University of Chinese Medicine, China
  4. Far Eastern Scientific Center of Physiology and Pathology of Respiration, Blagoveshchensk, Russian Federation
Cent Eur J Immunol 2025; 50 (3)
DOI: https://doi.org/10.5114/ceji.2025.154158
Online publish date: 2025/10/13
View full text Get citation
 
PlumX metrics:
Introduction
Excessive mucus secretion in airway epithelial cells is a hallmark of various airway inflammatory diseases. Neutrophil elastase (NE) is a recognized inducer of mucus secretion, yet the precise mechanisms underlying this process remain inadequately understood. This study aims to investigate the roles of myristoylated alanine-rich C-kinase substrate (MARCKS), activated CDC42 kinase 1 (ACK1) and cortactin in airway mucin secretion induced by NE.

Material and methods
Human airway epithelial cells were treated with NE following specific siRNA- mediated knockdown of MARCKS, ACK1 and cortactin. Western blotting and immunofluorescence were used to observe the expression and localization of cortactin, MARCKS and ACK1. The interaction between cortactin and ACK1 was analyzed using co-immunoprecipitation, and MUC5AC protein expression was measured using ELISA.

Results
NE stimulation only increased the phosphorylation levels of MARCKS, ACK1, and cortactin in the cells. Silencing MARCKS inhibited the phosphorylation of ACK1, and silencing ACK1 inhibited the phosphorylation of cortactin. Co-immunoprecipitation showed that ACK1 could directly bind to cortactin. The inhibition of MARCKS and cortactin significantly decreased the production of MUC5AC.

Conclusions
NE induces the phosphorylation of MARCKS, which subsequently facilitates the phosphorylation of ACK1. This cascade enhances the phosphorylation of cortactin, ultimately leading to increased mucus secretion. The MARCKS/ACK1/cortactin pathway is a potential therapeutic target for excessive mucus secretion induced by NE.

keywords:

airway epithelial cells, neutrophil elastase, mucin 5AC, myristoylated alanine-rich C-kinase substrate, activated CDC42 kinase 1, cortactin
Termedia
About us Contact
Copyright notice Privacy policy Advertising policy Contact us
Quick links
Journals Books eBooks Events
© 2025 Termedia Sp. z o.o.
Developed by Bentus.