IL-9 and IL-13 production by activated mast cells is strongly enhanced in the presence of lipopolysaccharide:: NF-κB is decisively involved in the expression of IL-9
IL-9 and IL-13 production by activated mast cells is strongly enhanced in the presence of lipopolysaccharide:: NF-κB is decisively involved in the expression of IL-9
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DOI：
10.4049/jimmunol.166.7.4391
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发表时间：
2001-04-01
影响因子：
4.4
通讯作者：
Schmitt, E
中科院分区：
文献类型：
--
作者：
Stassen, M;Müller, C;Schmitt, E
肥大细胞，由于其产生大量介质和细胞因子的能力，参与适应性和先天免疫的各种过程。在此，我们报告，在原代小鼠骨髓来源的肥大细胞激活离子霉素或IgE抗原的细菌内毒素LPS强烈增强IL-9和IL-13的表达，但不是IL-4。LPS的这种共刺激作用在来自LPS低反应小鼠品系BALB/c-LPSd的活化肥大细胞中不存在，尽管在这些细胞中促炎细胞因子IL-1仍然可以替代LPS。在IL-1存在下肥大细胞衍生的IL-13的产生增强是新的观察结果。肥大细胞与LPS的共活化导致NF-κ B的协同活化，这通过NF-κ B驱动的报告基因构建体显示。在存在NF-κ B活化抑制剂的情况下，IL-9的产生强烈降低，而IL-13的表达几乎不降低，并且IL-4的表达根本不受影响。NF-κ B通过IL-9启动子内的三个NF-κ B结合位点驱动IL-9的表达，我们使用凝胶位移分析和报告基因测定来表征。鉴于最近的报道强烈支持IL-9和IL-13在过敏性肺部炎症中的关键作用，我们的结果强调了LPS作为炎症过程中肥大细胞衍生的IL-9和IL-13产生的增强剂的潜在临床重要性反应和过敏性疾病。
Mast cells, due to their ability to produce a large panel of mediators and cytokines, participate in a variety of processes in adaptive and innate immunity. Herein we report that in primary murine bone marrow-derived mast cells activated with ionomycin or IgE-Ag the bacterial endotoxin LPS strongly enhances the expression of IL-9 and IL-13, but not IL-4. This costimulatory effect of LPS is absent in activated mast cells derived from the LPS-hyporesponsive mouse strain BALB/c-LPSd, although in these cells the proinflammatory cytokine IL-1 can still substitute for LPS. The enhanced production of mast cell-derived IL-13 in the presence of IL-1 is a novel observation. Coactivation of mast cells with LPS leads to a synergistic activation of NF-kappaB, which is shown by an NF-kappaB-driven reporter gene construct. In the presence of an inhibitor of NF-kappaB activation, the production of IL-9 is strongly decreased, whereas the expression of IL-13 is hardly reduced, and that of IL-4 is not affected at all. NF-kappaB drives the expression of IL-9 via three NF-kappaB binding sites within the IL-9 promoter, which we characterize using gel shift analyses and reporter gene assays. In the light of recent reports that strongly support critical roles for IL-9 and IL-13 in allergic lung inflammation, our results emphasize the potential clinical importance of LPS as an enhancer of mast cell-derived IL-9 and IL-13 production in the course of inflammatory reactions and allergic diseases.