ENHANCEMENT OF ENDOTOXIN-INDUCED INTERLEUKIN-10 PRODUCTION BY SR 31747A, A SIGMA-LIGAND
ENHANCEMENT OF ENDOTOXIN-INDUCED INTERLEUKIN-10 PRODUCTION BY SR 31747A, A SIGMA-LIGAND
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DOI：
10.1002/eji.1830251026
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发表时间：
1995-10-01
影响因子：
5.4
通讯作者：
CASELLAS, P
中科院分区：
文献类型：
--
作者：
BOURRIE, B;BOUABOULA, M;CASELLAS, P
SR 31747A是一种新的sigma配体，具有免疫抑制和抗炎特性。本研究表明，SR 31747A可显著增强脂多糖（LPS）诱导的全身白介素(IL)-10的释放，同时抑制肿瘤坏死因子(TNF)- α和干扰素(IFN)- γ的分泌。与此发现一致，我们还通过定量逆转录聚合酶链反应分析表明，SR 31747A增加了lps诱导的脾细胞中IL-10 mRNA的积累，而tnf - α和ifn - γ mRNA的水平均显著降低。SR 31747A处理对裸鼠和LPS处理的严重联合免疫缺陷小鼠IL-10产生的增强也很明显，清楚地表明T细胞和B细胞没有参与。最后，SR 31747A对LPS的致死作用具有保护作用。SR 31747A强烈刺激天然抗炎细胞因子IL-10的合成，这一特性在地塞米松中没有观察到，这一发现为该原始化合物的临床应用提供了新的见解，特别是在慢性炎症性疾病中，IL-10被认为是关键的调节成分。
SR 31747A is a new sigma ligand eliciting immunosuppressive and anti-inflammatory properties. Here, we show that SR 31747A greatly enhances lipopolysaccharide (LPS)-induced systemic release of interleukin (IL)-10, while it inhibits the secretion of tumor necrosis factor (TNF)-alpha and interferon (IFN)-gamma. In line with this finding, we also show by using quantitative reverse transcription-polymerase chain reaction analysis that SR 31747A increased LPS-induced IL-10 mRNA accumulation in spleen cells, whereas the level of both TNF-alpha and IFN-gamma mRNA was dramatically decreased. The enhancement of IL-10 production by SR 31747A treatment was also apparent in nude and severe-combined immunodeficient mice treated with LPS, clearly indicating that T and B cells were not involved. Finally, SR 31747A conferred protection against the lethal effect of LPS. The finding that SR 31747A strongly stimulates the synthesis of the natural anti-inflammatory cytokine IL-10, a property not observed with dexamethasone, provides new insights for the clinical use of this original compound, particularly in chronic inflammatory diseases where IL-10 is believed to be a pivotal regulatory component.