Mycoplasma hyopneumoniae induces pro-inflammatory cytokine and nitric oxide production through NFκB and MAPK pathways in RAW264.7 cells
Mycoplasma hyopneumoniae induces pro-inflammatory cytokine and nitric oxide production through NFκB and MAPK pathways in RAW264.7 cells
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DOI：
10.1007/s11259-010-9447-5
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发表时间：
2011-01-01
影响因子：
2.2
通讯作者：
Park, Seung-Chun
中科院分区：
文献类型：
--
作者：
Hwang, Mi-Hyun;Damte, Dereje;Park, Seung-Chun
在本研究中，我们证实了M。在小鼠巨噬细胞RAW 264.7细胞中，低密度脂蛋白诱导大量促炎细胞因子和一氧化氮（NO）的分泌。此外，M。通过ERK 1/2、p38和JNK/SAPK的磷酸化以及通过I κ B与NF-κ B的解离，hypopropioniae诱导MAPK和NF-κ B B途径的活化。通过蛋白质印迹和电迁移率变动分析证实转录因子NF-κ B的易位及其结合。根据这些结果，我们进一步假设这些信号蛋白参与了M。巨噬细胞中肺炎支原体诱导的促炎细胞因子和NO产生。因此，我们利用MAPK和NF-κ B B的特异性阻断剂，通过药理学方法研究参与细胞因子和NO产生的信号通路。结果表明MAPK抑制剂显著抑制TNF-α、IL-1 β、IL-6和NO。NF-κ B抑制剂PDTC显著抑制IL-1 β和NO的产生。这些发现有助于理解免疫反应的机制，并可能最终证明在开发新的治疗策略中是有用的。总之，我们发现了NF-κ B和MAPK信号通路参与M诱导的促炎细胞因子和NO上调的关键证据。下丘脑
In the present study, we confirmed the ability of M. hyopneumoniae to induce the secretion of large amount of proinflammatory cytokine and nitric oxide (NO) in murine macrophage RAW 264.7 cells. Moreover, M. hyopneumoniae-induced activation of the MAPK and NF-kappa B pathways by phosphorylation of ERK1/2, p38 and JNK/SAPK and by dissociation of I kappa B from NF-kappa B. Translocation of transcription factor NF-kappa B and its binding was confirmed through western blot and electromobility shift assay. From these results, we further hypothesized that these signal proteins were involved in M. hyopneumoniae-induced proinflammatory cytokines and NO productions in macrophages. Hence, we utilized specific blockers of MAPK and NF-kappa B to investigate the signaling pathway involvement in cytokine and NO production through pharmacological approaches. The results demonstrated significant inhibition of TNF-alpha, IL-1 beta, IL-6 and NO by MAPK inhibitors. NF-kappa B inhibitor PDTC significantly inhibited IL-1 beta and NO production. These findings contribute to the understanding of the mechanisms of immune reactivity and may ultimately prove useful in the development of new therapeutic strategies. In summary, we found critical evidence for the involvement of NF-kappa B and MAPK signaling pathways in the upregulation of proinflammatory cytokine and NO induced by M. hyopneumoniae.