Modulation of IL-8 Boosted by Mycoplasma pneumoniae lysate in Human Airway Epithelial Cells
Modulation of IL-8 Boosted by Mycoplasma pneumoniae lysate in Human Airway Epithelial Cells
复制标题
DOI：
10.1007/s10875-013-9909-y
复制
发表时间：
2013-08-01
影响因子：
9.1
通讯作者：
Sohn, Myung Hyun
中科院分区：
文献类型：
--
作者：
Lee, Kyung Eun;Kim, Kyung Won;Sohn, Myung Hyun
肺炎支原体是社区获得性肺炎的主要原因，已被认为是哮喘发病和加重的触发因素。呼吸道上皮细胞被M.由于局部炎症和刺激的宿主免疫应答，肺炎链球菌表现出许多细胞病变效应。我们研究了直接刺激M.肺炎克雷伯氏菌裂解物（MPL）在人气道上皮细胞中的表达。在人气道上皮细胞中，抗TLR 2单克隆抗体以剂量依赖性方式降低了MPLS诱导的IL-8蛋白，并被siRNA TLR 2显著阻断。ERK的药理学抑制剂U 0126和PD 98059有效地降低了IL-8的表达和ERK信号分子的活性形式，如通过抗磷酸化p44/42抗体检测到的。IL-8启动子中从-132到+41的区域显示出针对MPL的最高荧光素酶活性，并且NF-κ B和NF-IL 6的突变完全降低了活性。在研究NF-κ B和NF-IL 6报告载体的转染后，NF-IL 6活化被MPL刺激显著诱导，其被U 0126和单克隆抗TLR 2抗体显著降低。这些结果表明，与NF-κ B B相比，NF-IL 6在转录上更能调节MPLS诱导的IL-8增加。此外，NF-IL 6的活化受气道上皮细胞中的TLR 2和ERK信号通路的影响。
Mycoplasma pneumoniae, a major cause of community-acquired pneumonia, has been recognized as a trigger for asthma inception and exacerbation. The epithelial cells on the respiratory tract parasitized by M. pneumoniae exhibit a number of cytopathic effects as a result of local inflammation and stimulated host immune response. We investigated the interactions of signaling molecules regulating the release of IL-8 by the direct stimulation of M. pneumoniae lysate (MPL) in human airway epithelial cells. In human airway epithelial cells, MPL-induced IL-8 proteins were decreased by monoclonal anti-TLR2 antibody in a dose-dependent fashion, and significantly blocked by siRNA TLR2. The pharmacologic inhibitors of ERK, U0126 and PD98059, effectively reduced IL-8 expression and the active forms of ERK signaling molecules, as detected by anti-phosphorylated p44/42 antibody. The region spanning from -132 to +41 in the IL-8 promoter demonstrated the highest luciferase activity against MPL and the mutations of NF-kappa B and NF-IL6 entirely diminished the activity. After investigating transfections of the NF-kappa B and NF-IL6 reporter vectors, NF-IL6 activation was significantly induced by MPL stimulation, which was considerably decreased by U0126 and monoclonal anti-TLR2 antibody. These results indicate that MPL-induced IL-8 increase is transcriptionally regulated by NF-IL6 more than by NF-kappa B. Additionally, the activation of NF-IL6 is influenced by TLR2 and ERK signaling pathways in airway epithelial cells.