Human Langerhans-cell activation triggered in vitro by conditionally expressed MKK6 is counterregulated by the downstream effector RelB
Human Langerhans-cell activation triggered in vitro by conditionally expressed MKK6 is counterregulated by the downstream effector RelB
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DOI：
10.1182/blood-2006-05-022954
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发表时间：
2007-01-01
期刊：
影响因子：
20.3
通讯作者：
Strobl, Herbert
中科院分区：
文献类型：
--
作者：
Joergl, Almut;Platzer, Barbara;Strobl, Herbert
环境暴露的上皮朗格汉斯细胞（LC）遇到不同的先天性应激信号，这导致激活复杂的细胞内信号级联。其中，p38 MAPK是一贯磷酸化。LC激活触发P38信号传导的哪些方面是足够的仍有待阐明。我们表明，条件诱导的显性活性形式的MAPK激酶6（d.a.MKK6），直接上游激酶p38，在LC有效地诱导上调共刺激分子，并提高其T细胞刺激能力。这些即时效应显示对经典NF-κ B信号传导没有要求或仅要求很少。伴随着LC活化，d. a. MKK 6诱导替代NF-κ B成员RelB，其核定位标记成熟DC。在d.a.MKK6诱导的LC活化过程中，核RelB的特异性抑制进一步增强了它们的成熟状态。使用p38激活剂茴香霉素验证了这一观察结果，从而表明RelB调节的新型LC内在控制机制。
Environmentally exposed epithelial Langerhans cells (LCs) encounter diverse innate stress signals, which lead to the activation of complex intracellular signaling cascades. Among these, p38 MAPK is consistently phosphorylated. For which aspects of LC activation triggering of P38 signaling is sufficient remains to be elucidated. We show that conditional induction of a dominant active form of MAPK kinase 6 (d.a.MKK6), a direct upstream kinase of p38, in LCs efficiently induces the up-regulation of costimulatory molecules and enhances their T-cell stimulatory capacity. These immediate effects showed no or only a minor requirement for classical NF-kappa B signaling. Concomitant with LC activation, d.a.MKK6 induced the alternative NF-kappa B member RelB, whose nuclear localization marks mature DCs. Specific inhibition of nuclear RelB during d.a.MKK6-induced LC activation further enhanced their maturation state. This observation was validated using the p38 activator anisomycin, thus suggesting a novel LC intrinsic control mechanism regulated by RelB.