| 赵战芝，何钒，唐雅玲，孙慧.PF4通过NF-κB上调巨噬细胞MMP-9表达.[J].中南医学科学杂志.,2015,43(1):9-13. |
| PF4通过NF-κB上调巨噬细胞MMP-9表达 |
| Platelet Factor 4 Up-regulates the Expression of MatrixMetalloproteinase-9 in Macrophages via NF-κB |
| 投稿时间：2014-05-12 |
| DOI： |
| 中文关键词: 血小板因子4 基质金属蛋白酶9 巨噬细胞 核因子κB 动脉粥样硬化 |
| 英文关键词:platelet factor 4 matrix metalloproteinase-9 macrophages nuclear factor kappa B atherosclerosis |
| 基金项目:国家自然科学基金（81100214），南华大学博士启动基金（2012XQD40）. |
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| 中文摘要: |
| 目的观察血小板因子4（PF4）是否通过核因子κB（NF-κB）上调THP-1单核源性巨噬细胞基质金属蛋白酶9（MMP-9）表达。方法佛玻酯诱导THP-1细胞分化成巨噬细胞。巨噬细胞分别在NF-κB抑制剂（PDTC）缺乏或存在情况下与溶媒或PF4（100μg/L）孵育一定时间，RT-PCR检测MMP-9mRNA水平；同时，巨噬细胞与PF4（25～200μg/L）单独或结合Toll样受体4（TLR4）阻断剂（抗体HTA125，anti-TLR4）孵育，ELISA法检测NF-κB含量。结果PF4较对照组上调巨噬细胞MMP-9mRNA水平。而NF-κB抑制剂抑制PF4诱导的巨噬细胞MMP-9表达上调。PF4呈浓度依赖性增加巨噬细胞的NF-κB含量，最大效应浓度为100μg/L。TLR4阻断剂逆转PF4诱导的巨噬细胞NF-κB含量增加。结论PF4可能通过NF-κB上调巨噬细胞MMP-9的表达。TLR4可能是PF4-NF-κB通路中NF-κB的上游信号分子。 |
| 英文摘要: |
| Objective To investigate whether PF4 modulates the MMP-9 expression of macrophages via Nuclear factor kappa B（NF-κB）. Methods THP-1 monocytes were differentiated into monocyte-derived macrophages by phorbol 12-myristate 13-acetate （PMA）.Macrophages were incubated with PF4 （100 μg/L） in the absence or presence of NF-κB inhibitor pyrrolidine dithiocarbamate （PDTC）,the MMP-9 expression of macrophages was determined by Reverse-transcription polymerase chain reaction （RT-PCR）.Macrophages were incubated with PF4 （25-200 μg/L） or vehicle （PBS）,NF-κB content in cultured supernatant of macrophages was measured by ELISA assay.To evaluate the intracellular signal transduction pathways,macrophages were pretreated for 30min with the TLR4 blocker（monoclonal antibody HTA125，anti-TLR4） before the addition of PF4,NF-κB content was measured. Results Macrophages that were untreated showed a relatively low MMP-9 mRNA leveltreatment with PF4 increased MMP-9 expression.However,the high levels of MMP-9 expression induced by PF4 were significantly attenuated in the presence of NF-κB inhibitor.PF4 increased concentration of NF-κB in a dose dependent manner,with the strongest increase at 100ng/mL.The increased the concentration of NF-κB induced by PF4 was significantly reduced when treated with TLR4 blocker. Conclusion PF4 may up-regulate MMP-9 expression in macrophages via NF-κB.TLR4 may be upstream signaling molecules of NF-κB in PF4- NF-κB signaling pathway. |
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