Activation of the interleukin 6 gene by Mycobacterium tuberculosis or lipopolysaccharide is mediated by nuclear factors NF-IL6 and NF-kappa B.
Activation of the interleukin 6 gene by Mycobacterium tuberculosis or lipopolysaccharide is mediated by nuclear factors NF-IL6 and NF-kappa B.
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结核分枝杆菌或脂多糖对白介素 6 基因的激活是由核因子 NF-IL6 和 NF-kappa B 介导的。
DOI：
10.1073/pnas.91.6.2225
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发表时间：
1994
影响因子：
11.1
通讯作者：
Rom,WN
中科院分区：
文献类型：
--
作者：
Zhang,Y;Broser,M;Rom,WN
宿主对结核分枝杆菌的反应包括感染部位的肉芽肿形成和全身症状。在卡介苗（BCG）感染的动物模型中，通过免疫组织化学在肉芽肿中鉴定出细胞因子，这些细胞因子在受到分枝杆菌蛋白刺激时由单核吞噬细胞释放。在这方面，细胞因子白细胞介素6（IL-6）可能在结核感染的临床表现和病理事件中发挥作用。我们已经证明，脂阿拉伯甘露聚糖（LAM）从分枝杆菌细胞壁，这是几乎没有脂多糖（LPS），刺激单核吞噬细胞释放IL-6的剂量反应方式。LAM和LPS是外周血单核细胞IL-6基因表达的强诱导剂。通过缺失分析和氯霉素乙酰转移酶测定，LAM和LPS诱导的IL-6启动子活性均定位于DNA片段，位置-158至-49。在该片段中存在两个核因子NF-IL 6（位置-153至-145和-83至-75）和一个核因子NF-κ B（位置-72至-63）基序。IL-6启动子内的一个或多个这些基序的定点诱变证明，每个基序都具有正调控活性，并且它们可以以功能和方向独立的方式起作用。所有三个元件的缺失都消除了LAM和LPS对IL-6启动子活性的诱导作用。我们的结论是，NF-IL 6和NF-κ B位点介导IL-6诱导响应LPS和LAM，作为细菌或分枝杆菌的反应元件。
The host response to Mycobacterium tuberculosis includes granuloma formation at sites of infection and systemic symptoms. Cytokines have been identified by immunohistochemistry in granulomas in animal models of bacillus Calmette-Guérin (BCG) infection and are released by mononuclear phagocytes upon stimulation by mycobacterial proteins. In this regard, the cytokine interleukin 6 (IL-6) may play a role in the clinical manifestations and pathological events of tuberculosis infection. We have demonstrated that lipoarabinomannan (LAM) from the mycobacterial cell wall, which was virtually devoid of lipopolysaccharide (LPS), stimulated mononuclear phagocytes to release IL-6 in a dose-response manner. LAM and LPS were potent inducers of IL-6 gene expression in peripheral blood monocytes. Both LAM- and LPS-inducible IL-6 promoter activity was localized to a DNA fragment, positions -158 to -49, by deletion analysis and chloramphenicol acetyltransferase assay. Two nuclear factor NF-IL6 (positions -153 to -145 and -83 to -75) and one nuclear factor NF-kappa B (positions -72 to -63) motifs are present within this fragment. Site-directed mutagenesis of one or more of these motifs within the IL-6 promoter demonstrated that each has positive regulatory activity and that they could act in a function- and orientation-independent manner. Deletion of all three elements abolished inducibility of IL-6 promoter activity by both LAM and LPS. We conclude that the NF-IL6 and NF-kappa B sites mediate IL-6 induction in response to both LPS and LAM, acting as bacterial or mycobacterial response elements.
DOI：
10.1001/jama.1978.03280300074035
发表时间：
1978
期刊：
JAMA
影响因子：
--
作者：
L. Barton
通讯作者：
L. Barton