Related Experiment Video
Updated: Jun 21, 2026
Assessment of Respiratory Function in Conscious Mice by Double-chamber Plethysmography
Published on: July 10, 2018
p38 MAPK and MMP-9 cooperatively regulate mucus overproduction in mice exposed to acrolein fog
Dai-Shun Liu1, Tao Wang, Su-Xia Han
1Division of Pulmonary Diseases, State Key Laboratory of Biotherapy of China, West China Hospital of Sichuan University, Sichuan, China.
Objective:
To evaluate the role of p38 mitogen-activated protein kinase (MAPK) on mice airway inflammation, mucus production and the possible cross-talk between p38 MAPK and matrix metalloproteinase-9 (MMP-9) in mucin protein synthesis.
Methods:
Mice were exposed to 4.0 ppm of acrolein for 21 days with daily intraperitoneal injection of SB203580, a specific inhibitor of p38 MAPK. In control mice, sterile saline was administered instead. On days 7 and 21, mice were sacrificed to examine airway inflammation and mucus production by BALF cell counts, cytokine ELISA, and H&E and AB-PAS staining. The mRNA and protein levels of Muc5ac, p38 MAPK and MMP-9 in the lung were determined by RT-PCR, immunohistochemistry and Western blotting analysis. MMP-9 activity was measured by gelatin zymography.
Results:
Both the numbers of inflammatory cells and mucus-secreting goblet cells were significantly increased in the airways of mice exposed to acrolein as compared to the control mice. Acrolein-increased phosphorylation of p38 MAPK was significantly reduced by SB203580. The airway inflammation and goblet cell hyperplasia after acrolein challenge were also attenuated by SB203580 administration. Moreover, SB203580 treatment decreased the acrolein-induced increase of Muc5ac and MMP-9 expression and MMP-9 activity in airway epithelium.
Conclusions:
The results indicate an important role of p38 MAPK in acrolein-induced airway inflammation and mucus hypersecretion in mice. The cooperation of p38 and MMP-9 may contribute to the mucin overproduction after inflammatory challenge.
Insights
p38 mitogen-activated protein kinase (MAPK) drives airway inflammation and mucus production in mice exposed to acrolein. Inhibiting p38 MAPK with SB203580 reduced inflammation and mucin overproduction, suggesting a role for p38 MAPK and MMP-9 in airway disease.
Area of Science:
- Pulmonary Medicine
- Molecular Biology
- Toxicology
Background:
- Airway inflammation and mucus hypersecretion are key features of respiratory diseases.
- The p38 mitogen-activated protein kinase (MAPK) pathway is implicated in inflammatory responses.
- Matrix metalloproteinase-9 (MMP-9) plays a role in tissue remodeling and inflammation.
Purpose of the Study:
- To investigate the role of p38 MAPK in acrolein-induced airway inflammation and mucus production in mice.
- To explore the potential cross-talk between p38 MAPK and MMP-9 in mucin synthesis.
Main Methods:
- Mice were exposed to acrolein and treated with SB203580, a p38 MAPK inhibitor.
- Airway inflammation was assessed via bronchoalveolar lavage fluid cell counts and histology.
- Mucus production was evaluated using Periodic Acid-Schiff (PAS) staining.
- Gene and protein expression of Muc5ac, p38 MAPK, and MMP-9 were analyzed using RT-PCR, Western blotting, and immunohistochemistry.
- MMP-9 activity was measured by gelatin zymography.
Main Results:
- Acrolein exposure significantly increased airway inflammatory cells and mucus-secreting goblet cells.
- SB203580 treatment attenuated acrolein-induced airway inflammation and goblet cell hyperplasia.
- SB203580 reduced acrolein-induced increases in Muc5ac expression and MMP-9 activity.
- Acrolein-induced p38 MAPK phosphorylation was inhibited by SB203580.
Conclusions:
- p38 MAPK plays a critical role in acrolein-induced airway inflammation and mucus hypersecretion.
- The p38 MAPK and MMP-9 pathway may contribute to mucin overproduction following inflammatory challenges.
- Targeting p38 MAPK could be a therapeutic strategy for inflammatory airway diseases.
