Induction of matrix metalloproteinase-9 in alveolar macrophages by TNF-α through NF-κB signal pathwa

来源 :南京医科大学学报(英文版) | 被引量 : 0次 | 上传用户:Bo_Gao
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Objective: To explore the effect of tumor necrosis factor (TNF)-α on matrix metalloproteinase-9 (MMP-9)expression and activity in alveolar macrophages (AM) from patients with chronic obstructive pulmonary disease (COPD) and study its associated signal pathway. Methods: AM were collected from bronchoalveolar lavage fluid in patients with COPD. The AM were incubated for 1.5 h with pyrrolidine dithiocarbamate(PDTC)at concentrations from 0 μmol/L to 50 μmol/L and then stimulated for 24 h by TNF-α at 10 ng/ml. MMP-9 expression and activity were respectively detected by semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR), Western blotting and Zymography. NF-κB activity was investigated by electrophoretic mobility shift assay (EMSA).Results: Both the mRNA and protein levels of MMP-9 induced by TNF-α in AM were significantly elevated in a dose dependent manner (P < 0.05). The level of MMP-9 activity was also correspondingly significantly elevated in the induction ( P < 0.05), which was possibly related with the over-expression of MMP-9. NF-κB activity was significantly increased when AM were stimulated by 10 ng/mL TNF-α (P <0.05). The expression of MMP-9 induced by TNF-α could be significantly inhibited by PDTC ( P < 0.05). Conclusion: The expression and activity of MMP-9 from AM could be induced by TNF-α, and NF-κB signal pathway played an important role in the induction.
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