Study on the mechanism of pyrrolidine dithiocarbamate down-regulating matrix metalloproteinase-9 expression

Aim To study the effects of pyrrolidine dithiocarbamate(PDTC) on matrix metalloproteinase-9(MMP-9) expression in alveolar macrophages(AM) induced by TNF-α,and then to explore it's signal pathway.Methods AM were collected from bronchoalveolar lavage fluid in patients with chronic obstructive pulmonary disease.AM were pretreated with PDTC and then stimulated by TNF-α or IL-1.MMP-9 mRNA expression was detected by semi-quantitative reverse transcription-polymerase chain reaction and MMP-9 protein expression was detected by Western blot.Phospho-IκBα protein levels induced by TNF-α or IL-1 were detected by Western blot.NF-κB activity was detected by electrophoretic mobility shift assay.Results Both the mRNA and protein levels of MMP-9 induced by TNF-α in AM were significantly elevated in a dose dependent manner(P0.05).The expression of MMP-9 induced by TNF-α was significantly inhibited by PDTC(P0.05).PDTC had no clear effect of inhibiting the phosphorylation of IκBα induced by TNF-α or IL-1(P0.05).PDTC had distinct effect of inhibiting the activation of NF-κB induced by TNF-α or IL-1 in a dose-dependent manner(P0.05).It also showed PDTC couldn't directly inhibit NF-κB DNA binding activity in vitro(P0.05).Conclusions NF-κB plays an important role in MMP-9 expression induced by TNF-α in AM;PDTC can down-regulate MMP-9 expression induced by TNFα in AM possibly through preventing the degradation of IκBα via ubiquitylation-proteasome proteolytic pathway.