Wedelolactone suppresses LPS-induced caspase-11 expression by directly inhibiting the IKK Complex
Wedelolactone suppresses LPS-induced caspase-11 expression by directly inhibiting the IKK Complex
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DOI：
10.1038/sj.cdd.4401325
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发表时间：
2004-01-01
影响因子：
12.4
通讯作者：
Yuan, J
中科院分区：
文献类型：
--
作者：
Kobori, M;Yang, Z;Yuan, J
Caspase-11是促炎细胞因子IL-1 β成熟和病理性凋亡的关键调节因子。Caspase-11在正常条件下在大多数组织中不表达，但在病理刺激如脂多糖（LPS）存在下高度诱导。在这里，我们描述了鉴别和表征的wedelolactone，一种天然化合物，抑制LPS诱导的caspase-11在培养细胞中的表达，通过抑制NF-κ B介导的转录。我们证明，wedelolactone是IKK的抑制剂，IKK是通过介导IkappaB α的磷酸化和降解来激活NF-κ B的关键激酶。
Caspase-11 is a key regulator of proinflammatory cytokine IL-1beta maturation and pathological apoptosis. Caspase-11 is not expressed in most tissues under normal condition, but highly inducible upon pathological stimulation such as in the presence of lipopolysaccharide (LPS). Here, we describe the identification and characterization of wedelolactone, a natural compound that inhibits LPS-induced caspase-11 expression in cultured cells by inhibiting NF-kappaB-mediated transcription. We demonstrate that wedelolactone is an inhibitor of IKK, a kinase critical for activation of NF-kappaB by mediating phosphorylation and degradation of IkappaBalpha.