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.

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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