In vivo suppression of NF-kappa B and preservation of I kappa B alpha by interleukin-10 and interleukin-13
In vivo suppression of NF-kappa B and preservation of I kappa B alpha by interleukin-10 and interleukin-13
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DOI：
10.1172/jci119786
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发表时间：
1997-11-15
影响因子：
15.9
通讯作者：
Ward, PA
中科院分区：
文献类型：
--
作者：
Lentsch, AB;Shanley, TP;Ward, PA
IL-10和IL-13在体外和体内具有强大的抗肿瘤活性。在大鼠肺损伤的IgG免疫复合物模型中，外源性施用IL-10或IL-13最近已显示通过极大地抑制TNF α的肺产生来抑制中性粒细胞募集和随后的肺损伤。TNF α基因的转录控制受核因子κ B（NF-κ B）调节。NF-κ B B的激活涉及其胞质抑制剂I κ B α的降解，从而允许NF-κ B的核转位，并随之发生转录激活。在这项研究中，我们试图确定IL-10和IL-13在IgG免疫复合物诱导的肺损伤中的保护作用是否是通过抑制NF-κ B活化介导的。从肺泡巨噬细胞和整个肺组织的核提取物的电泳迁移率变化分析表明，IL-10和IL-13抑制NF-κ B B的核定位后，在体内沉积的IgE免疫复合物。Western blot分析表明，这些作用是由于肺泡巨噬细胞和全肺中I κ B α蛋白表达的保留。北方blot分析表明，在IgG免疫复合物的存在下，IL-10和IL-13增强了I κ B α mRNA的表达。这些发现表明，在体内，IL-10和IL-13可能通过保存I κ B α抑制NF-κ B B活化而起作用。
IL-10 and IL-13 have powerful antiinflammatory activities in vitro and in vivo, In the IgG immune complex model of lung injury in rats, exogenously administered IL-10 or IL-13 have recently been shown to suppress neutrophil recruitment and ensuing lung injury by greatly depressing pulmonary production of TNF alpha. Transcriptional control of the TNF alpha gene is regulated by the nuclear factor kappa B (NF-kappa B), Activation of NF-kappa B involves the degradation of its cytoplasmic inhibitor I kappa B alpha, allowing the nuclear translocation of NF-kappa B, with ensuing transcriptional activation. In this study, we sought to determine whether the protective effects of IL-10 and IL-13 in IgG immune complex-induced lung injury were mediated by inhibition of NF-kappa B activation. Electrophoretic mobility shift analysis of nuclear extracts from alveolar macrophages and whole lung tissues demonstrated that both IL-10 and IL-13 suppressed nuclear localization of NF-kappa B after in vivo deposition of Ige immune complexes. Western blot analysis indicated that these effects were due to preserved protein expression of I kappa B alpha in both alveolar macrophages and whole lungs, Northern blot analysis of lung mRNA showed that, in the presence of IgG immune complexes, IL-10 and IL-13 augmented I kappa B alpha mRNA expression. These findings suggest that in vivo, IL-10 and IL-13 may operate by suppressing NF-kappa B activation through preservation of I kappa B alpha.