Interleukin(IL)-36α and IL-36γ Induce Proinflammatory Mediators from Human Colonic Subepithelial Myofibroblasts.
Interleukin(IL)-36α and IL-36γ Induce Proinflammatory Mediators from Human Colonic Subepithelial Myofibroblasts.
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DOI：
10.3389/fmed.2015.00069
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发表时间：
2015
影响因子：
3.9
通讯作者：
Andoh A
中科院分区：
文献类型：
--
作者：
Kanda T;Nishida A;Takahashi K;Hidaka K;Imaeda H;Inatomi O;Bamba S;Sugimoto M;Andoh A
白细胞介素（IL）-36细胞因子是最近报道的IL-1细胞因子家族的成员。然而，关于IL-36细胞因子和肠道炎症之间的关联的信息很少。在本研究中，我们研究了IL-36α和IL-36γ的生物学活性，使用人结肠上皮下肌成纤维细胞（SEMF）。采用实时荧光定量聚合酶链反应和酶联免疫吸附试验分别检测SEMF中靶分子的mRNA表达和蛋白表达。使用蛋白质印迹分析和MyD 88衔接蛋白（MyD 88和IRAK 1）和NF-κB p65特异性小干扰RNA（siRNA）分析IL-36细胞因子的细胞内信号传导。IL-36α和IL-36γ显著增强SEMF分泌IL-6和CXC趋化因子（CXCL 1、CXCL 2和CXCL 8）。IL-36α/γ和IL-17 A或IL-36α/γ和肿瘤坏死因子-α的组合显示出对IL-6和CXC趋化因子的诱导的协同作用。IL-36α和/或IL-36γ诱导的促炎介质的mRNA表达被MyD 88或IRAK 1的siRNA转染显著抑制。丝裂原活化蛋白激酶抑制剂和NF-κ Bp 65特异性siRNA均显著降低IL-36α和/或IL-36γ诱导的IL-6和CXC趋化因子的表达。这些结果表明，IL-36α和IL-36γ通过诱导促炎介质参与肠道炎症。
Interleukin (IL)-36 cytokines are recently reported member of the IL-1 cytokine family. However, there is little information regarding the association between IL-36 cytokines and gut inflammation. In the present study, we investigated the biological activity of IL-36α and IL-36γ using human colonic subepithelial myofibroblasts (SEMFs). The mRNA expression and the protein expression of target molecules in SEMFs were evaluated using real-time polymerase chain reaction and enzyme-linked immunosorbent assay, respectively. The intracellular signaling of IL-36 cytokines was analyzed using Western blot analysis and small interfering RNAs (siRNAs) specific for MyD88 adaptor proteins (MyD88 and IRAK1) and NF-κB p65. IL-36α and IL-36γ significantly enhanced the secretion of IL-6 and CXC chemokines (CXCL1, CXCL2, and CXCL8) by SEMFs. The combination of IL-36α/γ and IL-17A or of IL-36α/γ and tumor necrosis factor-α showed a synergistic effect on the induction of IL-6 and CXC chemokines. The mRNA expression of proinflammatory mediators induced by IL-36α and/or IL-36γ was significantly suppressed by transfection of siRNA for MyD88 or IRAK1. Both inhibitors of mitogen activated protein kinases and siRNAs specific for NF-κBp65 significantly reduced the expression of IL-6 and CXC chemokines induced by IL-36α and/or IL-36γ. These results suggest that IL-36α and IL-36γ contribute to gut inflammation through the induction of proinflammatory mediators.