Enhanced interleukin-10 signaling with 14-member macrolides in lipopolysaccharide-stimulated macrophages
Enhanced interleukin-10 signaling with 14-member macrolides in lipopolysaccharide-stimulated macrophages
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在脂多糖刺激的巨噬细胞中使用 14 元大环内酯增强白细胞介素 10 信号传导
DOI：
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发表时间：
2008
期刊：
影响因子：
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通讯作者：
K. Yamauchi
中科院分区：
文献类型：
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作者：
S. Abe;S. Inoue;T. Ishikawa;I. Kubota;Y. Shibata;N. Takabatake;K. Yamauchi
据报道，14元大环内酯类药物（即红霉素（EM）和克拉霉素（CAM））对慢性呼吸道感染性疾病具有免疫调节作用。研究表明，14元大环内酯类药物对多种肺细胞如肺泡巨噬细胞具有免疫调节作用。白细胞介素（IL）-10是一种免疫调节细胞因子，主要通过选择性阻断促炎基因表达的机制，在负调节炎症方面发挥着不可替代的作用。它激活信号转导和转录激活因子（STAT）-3，随后诱导细胞因子信号转导抑制因子-3（SOCS-3），导致巨噬细胞中炎症反应的消退。然而，14元大环内酯类是否通过IL-10信号通路发挥免疫调节作用尚不清楚。我们的目的是评估14元大环内酯类是否影响IL-10信号通路。用EM或CAM预处理RAW264.7巨噬细胞系，并用脂多糖（LPS）刺激。用RT-PCR、ELISA和免疫印迹法测定IL-10、IL-10受体、磷酸化（p）STAT-3和SOCS-3的水平。我们观察到在处理的细胞中IL-10、p-STAT-3和SOCS-3的水平增加。此外，与对照细胞相比，在LPS刺激后6 h，溶媒处理的巨噬细胞和CAM处理的巨噬细胞的肿瘤坏死因子-α水平相等，但在LPS刺激后36 h，CAM处理的巨噬细胞的肿瘤坏死因子-α水平受到抑制。因此，14元大环内酯类药物可能部分通过增强IL-10/STAT-3/SOCS-3通路来启动炎症的早期消退。
Immunomodulatory effects of 14-member macrolides, namely erythromycin (EM) and clarithromycin (CAM), have been reported in chronic respiratory infectious diseases. It has been suggested that 14-member macrolides have immunomodulatory effects on various lung cells such as alveolar macrophages. Interleukin (IL)-10 is an immunomodulatory cytokine that performs an irreplaceable role in negatively regulating inflammation, primarily via a mechanism that selectively blocks the expression of pro-inflammatory genes. It activates signal transducer and activator of transcription (STAT)-3, and subsequently induces the suppressor of cytokine signaling-3 (SOCS-3), resulting in the resolution of inflammatory response in macrophages. However, it has been still unclear whether 14-member macrolides exert immunomodulatory effects via IL-10 signaling pathway. We aimed to evaluate whether 14-member macrolides affect the IL-10 signaling pathway. The RAW264.7 macrophage cell line was pretreated with EM or CAM, and stimulated with lipopolysaccharide (LPS). The levels of IL-10, IL-10 receptor, phosphorylated (p) STAT-3, and SOCS-3 were determined by RT-PCR, ELISA and immunoblotting. We observed increased levels of IL-10, p-STAT-3 and SOCS-3 in the treated cells. In addition, while the levels of tumor necrosis factor-α 6 h after LPS stimulation was equal between vehicle-treated and CAM-treated macrophage cells, those of CAM-treated cells were repressed 36 h following LPS stimulation, compared with those of the control cells. Therefore, the 14-member macrolides may initiate an early resolution of inflammation, in part, via the enhancement of the IL-10/STAT-3/SOCS-3 pathway.
影响因子：
32.4
作者：
Shibata, Y;Berclaz, PY;Trapnell, BC
通讯作者：
Trapnell, BC