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首页> 外文期刊>Molecular and Cellular Biology >Characterization of a functional NF-kappa B site in the human interleukin 1 beta promoter: evidence for a positive autoregulatory loop.
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Characterization of a functional NF-kappa B site in the human interleukin 1 beta promoter: evidence for a positive autoregulatory loop.

机译：人白介素1β启动子中功能性NF-κB位点的表征：阳性自动调节环的证据。

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The -300 region of the interleukin 1 beta (IL-1 beta) promoter contains a functional NF-kappa B binding site composed of the decamer sequence 5'-GGGAAAATCC-3'. Probes representing the -300 region or the NF-kappa B site alone interacted with NF-kappa B proteins present in phorbol myristate acetate-, lipopolysaccharide-, or Sendai virus-induced myeloid cell extracts as well as recombinant NFKB1 (p50) and RelA (p65); furthermore, NF-kappa B protein-DNA complex formation was dissociated in vitro by the addition of recombinant I kappa B alpha. Mutation of the NF-kappa B site in the context of the IL-1 beta promoter reduced the responsiveness of the IL-1 beta promoter to various inducers, including phorbol ester, Sendai virus, poly(rI-rC), and IL-1 beta. A 4.4-kb IL-1 beta promoter fragment linked to a chloramphenicol acetyltransferase reporter gene was also preferentially inducible by coexpression of individual NF-kappa B subunits compared with a mutated IL-1 beta promoter fragment. When multiple copies of the IL-1 beta NF-kappa B site were linked to an enhancerless simian virus 40 promoter, this element was able to mediate phorbol ester- or lipopolysaccharide-inducible gene expression. In cotransfection experiments, RelA (p65) and c-Rel (p85) were identified as the main subunits responsible for the activation of the IL-1 beta NF-kappa B site; also, combinations of NFKB1 (p50) and RelA (p65) or c-Rel and RelA were strong transcriptional activators of reporter gene activity. The presence of a functional NF-kappa B binding site in the IL-1 beta promoter suggests that IL-1 positively autoregulates its own synthesis, since IL-1 is a strong inducer of NF-kappa B binding activity. Thus, the IL-1 beta gene may be considered as an important additional member of the family of cytokine genes regulated in part by the NF-kappa B/rel family of transcription factors.
机译：白介素1β（IL-1β）启动子的-300区含有功能性的NF-κB结合位点，该结合位点由十聚体序列5'-GGGAAAATCC-3'组成。代表-300区或NF-κB位点的探针与佛波肉豆蔻酸酯乙酸脂，脂多糖或仙台病毒诱导的髓样细胞提取物中以及重组NFKB1（p50）和RelA（ p65）;此外，通过添加重组IκBα在体外解离了NF-κB蛋白-DNA复合物的形成。在IL-1 beta启动子的背景下NF-κB位点的突变降低了IL-1 beta启动子对各种诱导物的响应，包括佛波酯，仙台病毒，poly（rI-rC）和IL-1 Beta。与突变的IL-1β启动子片段相比，通过共表达单个NF-κB亚基还优选诱导与氯霉素乙酰转移酶报道基因连接的4.4-kbIL-1β启动子片段。当IL-1βNF-κB位点的多个副本与无增强猿猴病毒40启动子相连时，该元件能够介导佛波酯或脂多糖诱导的基因表达。在共转染实验中，RelA（p65）和c-Rel（p85）被鉴定为负责激活IL-1βNF-κB位点的主要亚基;同样，NFKB1（p50）和RelA（p65）或c-Rel和RelA的组合是报道基因活性的强转录激活因子。 IL-1 beta启动子中功能性NF-κB结合位点的存在表明IL-1积极自调其自身的合成，因为IL-1是NF-κB结合活性的强诱导剂。因此，IL-1β基因可以被认为是细胞因子基因家族的重要附加成员，该家族因子部分地受转录因子NF-κB/ rel家族的调节。

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