Platelet activating factor (PAF) antagonists on cytokine induction of iNOS and sPLA2 in immortalized astrocytes (DITNC).
Platelet activating factor (PAF) antagonists on cytokine induction of iNOS and sPLA2 in immortalized astrocytes (DITNC).
复制标题
血小板激活因子 (PAF) 拮抗剂对永生化星形胶质细胞 (DITNC) 中 iNOS 和 sPLA2 细胞因子诱导的影响。
DOI：
10.1023/a:1007550801444
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发表时间：
2000
影响因子：
4.4
通讯作者：
Sun,GY
中科院分区：
文献类型：
--
作者：
Wang,JH;Sun,GY
血小板活化因子(PAF)、1-O-alkyl-2-acetyl-sn-glycero-3-phosphocholine)及其受体在调节神经元的可塑性和炎症反应中发挥重要作用，特别是在神经元损伤过程中。PAF受体广泛分布于不同的脑区，存在于细胞表面和细胞内的膜室中。星形胶质细胞是免疫活性细胞，对细胞因子有反应，细胞因子刺激信号级联反应，导致基因转录激活和蛋白质合成。我们最近的研究表明，细胞因子，如肿瘤坏死因子-α(肿瘤坏死因子-α)、白介素1-β(IL-1β)和干扰素-γ(干扰素γ)能够诱导永生化星形胶质细胞诱导型一氧化氮合酶(INOS)和分泌型磷脂酶A2(SPLA2)基因(Li等，J.干扰素和细胞因子研究19：121-127)。1999年)。本研究的主要目的是检测PAF拮抗剂对细胞因子诱导性一氧化氮合酶和sPLA2的影响。结果表明，人工合成的PAF拮抗剂BN50730能剂量依赖性地抑制细胞因子诱导的NO产生和sPLA2的释放，而天然PAF拮抗剂BN52021则无此作用。BN50730对NO产生的抑制作用与iNOSmRNA和蛋白水平的降低以及NF-κB和STAT-1与DNA的结合密切相关，提示BN50730的作用位于转录过程的上游。这些结果与细胞内PAF在调节星形胶质细胞细胞因子信号通路中的作用是一致的，并进一步提示BN50730可能被用作抑制细胞因子诱导的炎症通路的治疗剂。
Platelet-activating factor (PAF, 1-O-alkyl-2-acetyl-sn-glycero-3-phosphocholine) and its receptor are known to play important roles in modulating neuronal plasticity and inflammatory responses, particularly during neuronal injury. PAF receptors are widespread in different brain regions and are present on the cell surface as well as in intracellular membrane compartments. Astrocytes are immune active cells and are responsive to cytokines, which stimulate signaling cascades leading to transcriptional activation of genes and protein synthesis. Our recent studies indicate the ability of cytokines, e.g., tumor necrosis factor-α (TNFα), interleukin-1β (IL-1β) and interferon-γ (IFNγ), to induce the inducible nitric oxide (iNOS) and secretory phospholipase A2(sPLA2) genes in immortalized astrocytes (DITNC) (Li et al., J. Interferon and Cytokine Res. 19: 121–127. 1999). The main objective for this study is to examine the effects of PAF antagonists on cytokine induction of iNOS and sPLA2in these cells. Results show that BN50730, a synthetic PAF antagonist, but not BN52021, a natural PAF antagonist (ginkolide B) can dose-dependently inhibit cytokine induction of NO production and sPLA2release. Inhibition of NO production by BN50730 corroborated well with the decrease in iNOS protein and mRNA levels as well as binding of NF-κB and STAT-1 to DNA, suggesting that BN50730 action is upstream of the transcriptional process. These results are in agreement with the role of intracellular PAF in regulating the cytokine signaling cascade in astrocytes and further suggest the possible use of BN50730 as a therapeutic agent for suppressing the inflammatory pathways elicited by cytokines.