Nuclear factor κB activity is essential for matrix metalloproteinase-1 and-3 upregulation in rabbit dermal fibroblasts

Nuclear factor κB activity is essential for matrix metalloproteinase-1 and-3 upregulation in rabbit dermal fibroblasts
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DOI:
10.1006/bbrc.1999.1551
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发表时间:
1999-10-22
影响因子:
3.1
通讯作者:
Newby, AC
Newby, AC
中科院分区:
生物学4区
文献类型:
--
作者:
Bond, M;Baker, AH;Newby, AC

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在增生性炎症过程中,包括伤口愈合和类风湿性关节炎,促炎细胞因子和生长因子上调了成纤维细胞中基质金属蛋白酶(MMPs)-1和-3的表达。激活蛋白-1 (AP-1)转录因子是必需的,但是,我们在这里表明,不足以上调,因为血小板衍生生长因子(PDGF)和碱性成纤维细胞生长因子(bFGF),它们强烈激活AP-1,但很少诱导MMP-1和-3。白细胞介素-1 α激活核因子κ B (nf - κ B),在bFGF或PDGF存在下协同上调MMP-1和-3的表达。腺病毒介导的I κ B α过表达,nf - κ B的抑制剂,完全抑制MMP-1和-3蛋白和mRNA的表达。因此,我们首次证明(nf - κ B)活性对于MMP-1和-3上调也是必不可少的。(C) 1999学术出版社。
Expression of matrix metalloproteinases (MMPs)-1 and -3 in fibroblasts is upregulated by pro-inflammatory cytokines and growth factors during proliferative inflammatory processes, including wound healing and rheumatoid arthritis. The Activator Protein-1 (AP-1) transcription factor is essential but, we show here, not sufficient for upregulation because platelet derived growth factor (PDGF) and basic fibroblast growth factor (bFGF), which strongly activate AP-1, poorly induce MMP-1 and -3. Interleukin-1 alpha, which activates nuclear factor-kappa B (NF-kappa B), synergistically upregulates MMP-1 and -3 expression in the presence of bFGF or PDGF. Adenovirus mediated overexpression of I kappa B alpha, the inhibitor of NF-kappa B, completely suppresses MMP-1 and -3 protein and mRNA expression. Hence, we show for the first time that (NF-kappa B) activity is also essential for MMP-1 and -3 upregulation. (C) 1999 Academic Press.