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Published on: October 22, 2019
[Tumor necrosis factor alpha-induced expression and activity of alveolar macrophages matrix metalloproteinase-9 in
Ya-qing Li1, Zhen-xiang Zhang, Yong-jian Xu
1Department of Respiratory Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
Objective:
To explore the expression and activity of matrix metalloproteinase-9 (MMP-9) from alveolar macrophages (AMs) induced by tumor necrosis factor-alpha (TNFalpha) in patients with chronic obstructive pulmonary disease (COPD), and therefore to study the possible mechanisms.
Methods:
AMs were collected from bronchoalveolar lavage fluid from patients with COPD, and then were stimulated for 24 h with TNFalpha at concentrations of 0.1 ng/ml, 1 ng/ml, 5 ng/ml, 10 ng/ml, and 20 ng/ml, respectively. The gene expression level of MMP-9 induced by TNFalpha was detected by semi-quantitative RT-PCR, and MMP-9 activity was measured by zymography. NF-kappaB activity was detected by electrophoretic mobility shift assay.
Results:
In unstimulated AMs, the densitometry unit rate of MMP-9 mRNA to beta-actin mRNA was 0.1826 +/- 0.0084. When AMs were stimulated by TNFalpha at concentrations of 0.1 ng/ml, 1 ng/ml, 5 ng/ml, 10 ng/ml, and 20 ng/ml, the densitometry unit rates of MMP-9 mRNA to beta-actin mRNA were 0.4279 +/- 0.0204, 0.5431 +/- 0.0058, 0.6185 +/- 0.0208, 0.6859 +/- 0.0080, and 0.7784 +/- 0.0208, respectively. In unstimulated AMs, the densitometry unit of active MMP-9 was 10 227 +/- 738, but when AMs were stimulated by TNFalpha at concentrations of 0.1 ng/ml, 1 ng/ml, 5 ng/ml, 10 ng/ml, and 20 ng/ml, the densitometry units of active MMP-9 were 40,528 +/- 974, 113,741 +/- 4547, 190,696 +/- 4032, 309,505 +/- 7639, and 427,305 +/- 9145, respectively. NF-kappaB activity was significantly elevated after AMs were stimulated by TNFalpha at the concentration of 10 ng/ml (P < 0.05).
Conclusions:
The expression and activity of MMP-9 can be induced by TNFalpha, and the induction was possibly related with the NF-kappaB-mediated signal transduction pathway.
Insights
Tumor necrosis factor-alpha (TNFalpha) significantly increases matrix metalloproteinase-9 (MMP-9) expression and activity in alveolar macrophages from COPD patients. This induction is linked to the NF-kappaB signaling pathway, suggesting a potential therapeutic target.
Area of Science:
- Pulmonary Medicine
- Molecular Biology
- Immunology
Context:
- Chronic obstructive pulmonary disease (COPD) is a major health concern characterized by chronic airway inflammation.
- Alveolar macrophages (AMs) play a critical role in COPD pathogenesis.
- Matrix metalloproteinase-9 (MMP-9) is implicated in tissue remodeling and inflammation in COPD.
Purpose:
- To investigate the effect of tumor necrosis factor-alpha (TNFalpha) on MMP-9 expression and activity in AMs from COPD patients.
- To elucidate the underlying molecular mechanisms, specifically the role of NF-kappaB signaling.
Summary:
- AMs from COPD patients were stimulated with varying concentrations of TNFalpha.
- MMP-9 gene expression and activity were significantly upregulated by TNFalpha in a dose-dependent manner.
- NF-kappaB activation was observed at higher TNFalpha concentrations, suggesting its involvement in the pathway.
Impact:
- This study demonstrates that TNFalpha induces MMP-9 in COPD AMs, potentially contributing to disease progression.
- The findings highlight the NF-kappaB pathway as a key mediator, offering a potential target for novel COPD therapies.
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