TNF-α Up-regulates matrix metalloproteinase-9 expression and activity in alveolar macrophages from patients with chronic obstructive pulmonary disease

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.