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TNF-alpha up-regulates matrix metalloproteinase-9 expression and activity in alveolar macrophages from patients with
Yaqing Li1, Zhenxiang Zhang, Yongjian Xu
1Department of Respiratory Medicine, Zhejiang Provincial People's Hospital, Hangzhou 310014, China.
Abstract:
To study the effects of tumor necrosis factor (TNF)-alpha on matrix metalloproteinase (MMP)-9 expression and activity in alveolar macrophages (AM) and to investigate the role of NF-kappaB in the induction, AM were collected from bronchoalveolar lavage fluid (BALF) of healthy subjects and patients with chronic obstructive pulmonary disease (COPD). MMP-9 expression and activity were detected by semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR), Western blotting and zymography. NF-kappaB activity was detected by electrophoretic mobility shift assay (EMSA). MMP-9 expression and activity induced by TNF-alpha in AM from healthy subjects or patients with COPD were significantly increased in a dose-dependent manner (P<0.05). NF-kappaB activity induced by TNF-alpha was significantly increased in AM from patients with COPD, and pyrrolidine dithiocarbamate (PDTC) and N-acetyl-L-cysteine (NAC) significantly inhibited the activation of NF-kappaB induced by TNF-alpha (P<0.05). The presents study suggested that the expression and activity of MMP-9 from AM can be induced by TNF-alpha, and TNF-alpha/NF-kappaB signal pathway may play an important role in the induction.
Insights
Tumor necrosis factor-alpha (TNF-alpha) increases matrix metalloproteinase-9 (MMP-9) in lung cells. The TNF-alpha/NF-kappaB pathway is key in this MMP-9 induction, particularly in chronic obstructive pulmonary disease.
Area of Science:
- Pulmonary Medicine
- Cellular Biology
- Immunology
Background:
- Matrix metalloproteinase-9 (MMP-9) plays a role in lung tissue remodeling.
- Alveolar macrophages (AM) are crucial immune cells in the lungs.
- Chronic obstructive pulmonary disease (COPD) involves lung inflammation and tissue damage.
Purpose of the Study:
- To investigate the effect of tumor necrosis factor-alpha (TNF-alpha) on MMP-9 expression and activity in AM.
- To explore the involvement of the NF-kappaB signaling pathway in TNF-alpha-induced MMP-9 production.
Main Methods:
- AM were isolated from bronchoalveolar lavage fluid (BALF) of healthy individuals and COPD patients.
- MMP-9 expression and activity were assessed using RT-PCR, Western blotting, and zymography.
- NF-kappaB activity was measured by electrophoretic mobility shift assay (EMSA).
Main Results:
- TNF-alpha significantly upregulated MMP-9 expression and activity in AM from both healthy subjects and COPD patients in a dose-dependent manner.
- TNF-alpha markedly increased NF-kappaB activity in AM from COPD patients.
- Inhibitors pyrrolidine dithiocarbamate (PDTC) and N-acetyl-L-cysteine (NAC) significantly reduced TNF-alpha-induced NF-kappaB activation.
Conclusions:
- TNF-alpha induces MMP-9 expression and activity in alveolar macrophages.
- The TNF-alpha/NF-kappaB signaling pathway is critically involved in mediating TNF-alpha-induced MMP-9 production in AM.
- This pathway may be a significant factor in the pathogenesis of COPD.
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