Related Experiment Video
Updated: May 15, 2026
An IL-8 Transiently Transgenized Mouse Model for the In Vivo Long-term Monitoring of Inflammatory Responses
Published on: July 7, 2017
A novel function of MUC18: amplification of lung inflammation during bacterial infection
Qun Wu1, Stephanie R Case, Maisha N Minor
1Pulmonary Division, Department of Medicine, National Jewish Health, Denver, Colorado 80206, USA.
Abstract:
Bacterial infection plays a critical role in exacerbations of various lung diseases, including chronic pulmonary obstructive disease (COPD) and asthma. Excessive lung inflammation is a prominent feature in disease exacerbations, but the underlying mechanisms remain poorly understood. Cell surface glycoprotein MUC18 (alias CD146 or melanoma cell adhesion molecule) has been shown to promote metastasis in several tumors, including melanoma. We explored the function of MUC18 in lung inflammatory responses to bacteria (eg, Mycoplasma pneumoniae) involved in lung disease exacerbations. MUC18 expression was increased in alveolar macrophages from lungs of COPD and asthma patients, compared with normal healthy human subjects. Mouse alveolar macrophages also express MUC18. After M. pneumoniae lung infection, Muc18(-/-) mice exhibited lower levels of the lung proinflammatory cytokines KC and TNF-α and less neutrophil recruitment than Muc18(+/+) mice. Alveolar macrophages from Muc18(-/-) mice produced less KC than those from Muc18(+/+) mice. In Muc18(-/-) mouse alveolar macrophages, adenovirus-mediated MUC18 gene transfer increased KC production. MUC18 amplified proinflammatory responses in alveolar macrophages, in part through enhancing the activation of nuclear factor-κB (NF-κB). Our results demonstrate, for the first time, that MUC18 exerts a proinflammatory function during lung bacterial infection. Up-regulated MUC18 expression in lungs (eg, in alveolar macrophages) of COPD and asthma patients may contribute to excessive inflammation during disease exacerbations.
Insights
MUC18, a cell surface glycoprotein, promotes inflammation in lung bacterial infections. Its increased expression in COPD and asthma patients may worsen lung inflammation during exacerbations.
Area of Science:
- Immunology
- Pulmonary Medicine
- Molecular Biology
Background:
- Bacterial infections trigger lung disease exacerbations like COPD and asthma.
- Excessive lung inflammation is key in exacerbations, but mechanisms are unclear.
- MUC18 (CD146) is known for tumor metastasis, its role in lung inflammation is unexplored.
Purpose of the Study:
- To investigate the function of MUC18 in lung inflammatory responses to bacterial infection.
- To determine MUC18's role in exacerbations of chronic pulmonary obstructive disease (COPD) and asthma.
Main Methods:
- Compared MUC18 expression in alveolar macrophages from healthy subjects and patients with COPD/asthma.
- Infected wild-type and MUC18-deficient mice with Mycoplasma pneumoniae.
- Analyzed cytokine production (KC, TNF-α) and neutrophil recruitment.
- Utilized adenovirus-mediated gene transfer to restore MUC18 in knockout macrophages.
- Assessed nuclear factor-kappa B (NF-κB) activation.
Main Results:
- MUC18 expression was elevated in alveolar macrophages of COPD and asthma patients.
- MUC18-deficient mice showed reduced lung inflammation (lower KC, TNF-α) and neutrophil influx post-infection.
- MUC18-deficient macrophages produced less KC; MUC18 gene transfer restored KC production.
- MUC18 enhanced macrophage proinflammatory responses, partly via NF-κB activation.
Conclusions:
- MUC18 has a proinflammatory role in lung bacterial infections.
- Upregulated MUC18 in lung macrophages may contribute to excessive inflammation in COPD and asthma exacerbations.
