Expression and regulation of inducible IκB kinase (IKK-i) in human fibroblast-like synoviocytes
Expression and regulation of inducible IκB kinase (IKK-i) in human fibroblast-like synoviocytes
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DOI：
10.1006/cimm.2002.1885
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发表时间：
2001-11-25
影响因子：
4.3
通讯作者：
Firestein, GS
中科院分区：
文献类型：
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作者：
Aupperle, KR;Yamanishi, Y;Firestein, GS
IkappaB激酶(IKK)在核因子kappaB(NF-kappaB)的调节中起着关键作用。我们先前证实了两种激酶IKK1和IKK2在成纤维样滑膜细胞(FLS)中的表达，并确定了它们在体外和体内对炎性基因表达的功能影响。最近，一种新的可诱导的IkappaB激酶被描述，即IKK-I或IKK-epsilon，它在功能和结构上不同于结构性表达的IKK1和IKK2。因此，我们研究了这种新的激酶在类风湿性关节炎和骨性关节炎患者的FLS中的表达和调节。有趣的是，在所有被检测的细胞系中都观察到了构成基因和蛋白质的表达。刺激24 h后，FLS中IKK-I的表达增加了7.2+/-1.8倍(P<；0.02)。IL-1还显著增加了IKK-I基因的表达。时程实验表明，在TNFpha刺激3h内，IKK-I基因表达增加，并持续至少24小时，剂量-反应研究表明，低至1 ng/ml的TNFpha可促进IKK-I基因表达。在类风湿性关节炎、骨性关节炎和正常滑膜中也发现了结构性IKK-1基因的表达。这是首次报道在原代人类滑膜细胞中表达这种新的蛋白，并对其进行细胞因子调控。(C)2001年埃尔塞维尔科学公司(美国)。
IkappaB kinase (IKK) plays a key role in the regulation of nuclear factor kappaB (NF-kappaB). We previously demonstrated the expression of two kinases, IKK1 and IKK2, in fibroblast-like synoviocytes (FLS) and determined their functional consequences for inflammatory gene expression in vitro and in vivo. Recently, a novel inducible IkappaB kinase has been described, namely, IKK-i or IKK-epsilon, which is functionally and structurally distinct from constitutively expressed IKK1 and IKK2. Therefore, we investigated the expression and regulation of this novel kinase in FLS from patients with rheumatoid arthritis and osteoarthritis. Interestingly, constitutive gene expression and protein expression were observed in all cell lines examined. TNFalpha stimulation for 24 h increased IKK-i expression 7.2 +/- 1.8-fold in FLS (P < 0.02). IL-1 also significantly increased IKK-i gene expression. Time course experiments demonstrated that IKK-i gene expression increased within 3 h of TNFalpha stimulation and persisted for at least 24 h. Dose-response studies showed that as little as 1 ng/ml of TNFalpha increased IKK-i gene expression. Constitutive IKK-1 gene expression was also noted in rheumatoid arthritis, osteoarthritis, and normal synovium. This is the first report demonstrating constitutive expression and cytokine regulation of this novel kinase in primary human synovial cells. (C) 2001 Elsevier Science (USA).