TGF-β1 inhibits NF-κB activity through induction of IκB-α expression in human salivary gland cells:: A possible mechanism of growth suppression by TGF-1β
TGF-β1 inhibits NF-κB activity through induction of IκB-α expression in human salivary gland cells:: A possible mechanism of growth suppression by TGF-1β
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DOI：
10.1006/excr.1999.4503
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发表时间：
1999-07-10
影响因子：
3.7
通讯作者：
Sato, M
中科院分区：
文献类型：
--
作者：
Azuma, M;Motegi, K;Sato, M
转化生长因子(TGF)- β是参与抑制多种上皮细胞增殖的一个大的信号分子超家族的原型。尽管积累的证据表明tgf - β在多种细胞类型中的抗生核作用机制，但tgf - β调节nf - κ B转录因子的信号转导机制在很大程度上是未知的。由于NF-kappa B不仅参与炎症反应，而且还介导细胞生长，我们研究了tgf - β 1对NF-kappa B活性的影响以及抑制I -kappa B- α蛋白在人唾液腺细胞克隆NS-SV-AC、HSGc和cl-1生长中的作用。NF-kappa B通常通过与I -kappa B的蛋白-蛋白相互作用而保持失活状态，但在唾液腺细胞系中被发现具有组成性活性。tgf - β 1处理细胞克隆后，NF-kappa B活性在NS-SV-AC和HSGc中被抑制，但在缺乏tgf - β II型受体表达的cl-1中未被抑制。在NS-SV-AC和HSGc中，这种抑制是通过在mRNA和蛋白水平上诱导I κ pa b - α介导的。用特定的反义寡核苷酸阻断nf - κ B亚基可降低包括cl-1在内的所有细胞克隆的生长速度。在NS-SV-AC中引入突变形式的I κ B- α cDNA抑制了该细胞克隆的生长速度。这些结果表明，tgf - β 1通过诱导人唾液腺细胞中I κ B- α的表达下调nf - κ B的活性，抑制nf - κ B活性抑制了这些细胞的生长速度。(C) 1999学术出版社。
Transforming growth factor (TGF)-beta is the prototype of a large superfamily of signaling molecules involved in the inhibition of proliferation of multiple epithelial cell types. Although accumulated evidence indicates the mechanisms of the antimitogenic effect of TGF-beta in a variety of cell types, the signal transduction mechanism underlying the regulation of NF-kappa B transcription factor by TGF-beta is largely unknown. Because NF-kappa B is not only involved in inflammatory responses but also mediates cell growth, we have investigated the effect of TGF-beta 1 on the activity of NF-kappa B and the role of the inhibitory I kappa B-alpha protein in the growth of the human salivary gland cell clones NS-SV-AC, HSGc, and cl-1. NF-kappa B, which is usually maintained in an inactive state by protein-protein interaction with I kappa B, was found to be constitutively active in salivary gland cell lines. Upon treatment of cell clones with TGF-beta 1, the NF-kappa B activity in NS-SV-AC and HSGc, but not in cl-1, which lacks the expression of TGF-beta type II receptor, was suppressed. In NS-SV-AC and HSGc, this inhibition was mediated by the induction of I kappa B-alpha at the mRNA and protein levels. The blocking of NF-kappa B subunit with a specific antisense oligonucleotide reduced the growth rate of all of the cell clones, including cl-1. Introduction of a mutated form of I kappa B-alpha cDNA into NS-SV-AC suppressed the growth rate of this cell clone, These results indicate that TGF-beta 1 downregulates NF-kappa B activity through the induction of I kappa B-alpha expression in human salivary gland cells and that inhibition of NF-kappa B activity suppresses the growth rate of these cells. (C) 1999 Academic Press.