Study on the mechanism of pyrrolidine dithiocarbamate down-regulating matrix metalloproteinase-9 expression
- VernacularTitle:吡咯烷二硫代氨基甲酸盐下调基质金属蛋白酶9表达机制的研究
- Author:
Yaqing LI
;
Zhenxiang ZHANG
- Publication Type:Journal Article
- Keywords:
nuclear factor-kappaB;
pyrrolidine dithiocarbamate;
matrix metalloproteinase;
I?B?
- From:
Chinese Pharmacological Bulletin
1987;0(01):-
- CountryChina
- Language:Chinese
-
Abstract:
Aim To study the effects of pyrrolidine dithiocarbamate(PDTC) on matrix metalloproteinase-9(MMP-9) expression in alveolar macrophages(AM) induced by TNF-?,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-? 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-I?B? protein levels induced by TNF-? or IL-1 were detected by Western blot.NF-?B activity was detected by electrophoretic mobility shift assay.Results Both the mRNA and protein levels of MMP-9 induced by TNF-? in AM were significantly elevated in a dose dependent manner(P0.05).PDTC had distinct effect of inhibiting the activation of NF-?B induced by TNF-? or IL-1 in a dose-dependent manner(P0.05).Conclusions NF-?B plays an important role in MMP-9 expression induced by TNF-? in AM;PDTC can down-regulate MMP-9 expression induced by TNF? in AM possibly through preventing the degradation of I?B? via ubiquitylation-proteasome proteolytic pathway.