白细胞介素10对巨噬细胞源泡沫细胞趋化因子表达的影响

The Effects of Interleukin-10 on Chemokine mRNA Expression in Monocyte-Macrophage Derived Foam Cells

目的探讨白细胞介素10对单核—巨噬细胞源性泡沫细胞转化过程中趋化因子表达的影响及其机制。方法以佛波醇酯诱导THP-1单核细胞分化为巨噬细胞,在氧化型低密度脂蛋白作用下形成泡沫细胞,同时给予白细胞介素10干预,采用逆转录聚合酶链反应和凝胶阻滞试验研究单核细胞趋化蛋白1、巨噬细胞炎性蛋白5、白细胞介素8mRNA的表达变化及白细胞介素10对核因子κB活性的影响。结果在白细胞介素10作用下,泡沫细胞中单核细胞趋化蛋白1和巨噬细胞炎性蛋白5mRNA相对表达量均显著降低,且与作用时间成正相关,而白细胞介素8相对表达量变化不明显。同时白细胞介素10能显著抑制氧化型低密度脂蛋白诱导的核因子κB活化。结论白细胞介素10选择性抑制单核—巨噬细胞源性泡沫细胞形成中趋化因子mRNA的表达与有效地抑制核因子κB活性密切相关。这对降低炎症反应,减少泡沫细胞形成,延缓动脉粥样斑块形成具有重要意义。

Aim To investigate intedeukin-10 （IL-10） affecting chemokine mRNA expression in monocyte-macrophage derived foam cells and its mechanism, Methods Macrophage was induced by phogrbol myristate acetate （PMA） forming THP-1 cell, and then the cells were further stimulated by oxidized low density lipoprotein with or without IL-10. The influence by IL-10 on chemokine mRNA expression was observed by reverse transcription-polymerase chain reaction （RT-PCR） and the nuclear factor-roB （NF-κB） activation was observed by electrophoretic mobility shift assay （EMSA）. Results IL-10 could selectively inhibit monocyte chemoattractant protein-1 （MCP-1 ） and macrophage inflammatory protein-5 （MIP-5） mRNA expression. The effects were in dose-dependent fashion. However there was no effect on IL-8 mRNA expression. IL-10 could also significantly inhibit ox-LDL induced NF-κB activation. Conclusions The inhibition on NF-κB activation induced by IL-10 is responsible for decreasing MCP- 1 and MIP-5 mRNA expression. The reduction of chemokine expression at the site of atherosclerotic plaque might cut down inflammatory cells recruitment and reduce the plaque further formation.