Cytokine production through PKC/p38 signaling pathways, not through JAK/STAT1 pathway, in mast cells stimulated with IFNgamma.
Cytokine production through PKC/p38 signaling pathways, not through JAK/STAT1 pathway, in mast cells stimulated with IFNgamma.
复制标题
在 IFNγ 刺激的肥大细胞中，细胞因子通过 PKC/p38 信号通路产生，而不是通过 JAK/STAT1 通路。
DOI：
10.1016/j.cyto.2008.12.008
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发表时间：
2009
期刊：
影响因子：
3.8
通讯作者：
J. Ro
中科院分区：
文献类型：
--
作者：
J. Seo;D. Kim;Yun;J. Ro
干扰素γ与肥大细胞相关疾病密切相关。干扰素γ抑制肥大细胞脱颗粒作用的研究报道较多。然而，干扰素γ刺激肥大细胞产生炎性细胞因子的研究尚不清楚。因此，我们旨在研究干扰素γ刺激肥大细胞产生细胞因子的信号通路。用100个单位的干扰素γ刺激人肥大细胞系HMC-1或小鼠骨髓来源的肥大细胞。分别用ELISA法和RT-PCR法检测细胞因子蛋白和mRNAs的表达，免疫印迹法检测MAP激酶、PKC、JAK1/2和STAT1在酪氨酸701和丝氨酸727上的活性，用凝胶迁移率改变法检测转录因子的DNA结合活性。干扰素γ刺激后，肥大细胞炎性细胞因子的蛋白和mRNAs表达增加，MAP激酶、蛋白激酶Cα和βI、JAK1/2和STAT1在酪氨酸701和丝氨酸727上的磷酸化增加。与单纯干扰素κ刺激相比，JAK抑制剂或蛋白激酶C抑制剂可抑制丝氨酸727上p38激酶、STAT1的磷酸化，抑制NF-γB和AP-1的活性。这些结果表明，干扰素γ刺激的肥大细胞通过PKC/p38/NF-κB和AP-1途径诱导炎性细胞因子的产生，而不是通过经典的JAK/STAT1途径。
IFNγ is strongly related to mast cell-associated diseases. There are many reports that IFNγ inhibits mast cell degranulation. However, inflammatory cytokine production in mast cells stimulated with IFNγ has not yet been clearly investigated. Therefore, we aimed to investigate the signaling pathways of cytokine production in mast cells stimulated with IFNγ. Human mast cell line (HMC)-1 or mouse bone marrow-derived mast cells (BMMCs) were stimulated with IFNγ (100units) for time periods indicated. Expressions of proteins and mRNAs of cytokines were determined by ELISA and RT-PCR, respectively, activities of MAP kinases, PKC, JAK1/2, and STAT1 on tyrosine 701 and serine 727 by immunoblotting, the DNA-binding activity of the transcription factors by electrophoretic mobility shift assay. IFNγ-stimulated mast cells showed increase in expressions of proteins and mRNAs of inflammatory cytokines, phosphorylations of MAP kinases, PKCα and βI, JAK1/2, and STAT1 on tyrosine 701 and serine 727. JAK inhibitor or PKC inhibitors inhibited the phosphorylations of p38 kinase, STAT1 on serine 727, and activities of NF-κB and AP-1 compared to IFNγ stimulation alone. These data suggest that IFNγ-stimulated mast cells induce productions of inflammatory cytokines through PKC/p38/NF-κB and AP-1 pathways, not through classical JAK/STAT1 pathway, in both mast cells.