Interleukin-3 stimulates migration and proliferation of vascular smooth muscle cells - A potential role in atherogenesis
Interleukin-3 stimulates migration and proliferation of vascular smooth muscle cells - A potential role in atherogenesis
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DOI：
10.1161/01.cir.103.4.549
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发表时间：
2001-01-30
期刊：
影响因子：
37.8
通讯作者：
Pegoraro, L
中科院分区：
文献类型：
--
作者：
Brizzi, MF;Formato, L;Pegoraro, L
由活化的T淋巴细胞释放的细胞因子是慢性炎症反应（包括动脉粥样硬化）的关键调节因子。本研究的目的是研究白细胞介素-3（IL-3）在浸润动脉粥样硬化斑块的淋巴细胞中的存在以及这种细胞因子对原代血管平滑肌细胞（SMCs）的影响。方法和结果20例动脉粥样硬化颈动脉标本和5例颈内动脉早期动脉粥样硬化病变被手动切碎成碎片，在固相抗CD 3聚苯乙烯板上分离浸润动脉粥样硬化斑块的T淋巴细胞。Southern杂交分析表明，在所有样品中。淋巴细胞表达IL-3和IL-2受体α链转录物，表明在这种情况下，活化的T淋巴细胞可能释放IL-3。我们进一步分析了IL-3受体的表达和配体对血管平滑肌细胞的生物学效应。β-IL-3转导亚单位在培养的SMC和动脉粥样硬化内的内皮细胞和SMC上均被检测到。对IL-3诱导的生物学效应的分析表明，它能够触发促有丝分裂和促运动信号。此外，我们证明了加入PD 98059，一种已知的MAP-细胞外信号调节/MAP激酶途径的抑制剂，完全抑制IL-3介导的MAP激酶活化和IL-3诱导的迁移和增殖。终于来了IL-3被发现刺激血管内皮生长因子（VEGF）基因transcription. Conclusions IL-3，表达的活化T淋巴细胞浸润早期和先进的动脉粥样硬化斑块，可以维持动脉粥样硬化的过程中，无论是直接，通过激活SMC的迁移和增殖，或间接，通过VEGF的生产。
Background-Cytokines released by activated T lymphocytes are key regulators of chronic inflammatory response, including atherosclerosis. The aim of this study was to investigate the presence of interleukin-3 (IL-3) in lymphocytes infiltrating the atherosclerotic plaque and the effect of this cytokine on primary vascular smooth muscle cells (SMCs).Methods and Results-Twenty atherosclerotic carotid arterial specimens and 5 early atherosclerotic lesions from the internal carotid were manually minced to fragments, and T lymphocytes infiltrating the atherosclerotic plaque were isolated on solid-phase anti-CD3 polystyrene plates. Southern blot analysis demonstrated that in all samples. lymphocytes expressed IL-3 and IL-2 receptor alpha -chain transcripts, indicating that in this context, the activated T lymphocytes may release IL-3. We further analyzed the expression of the IL-3 receptor and the biological effects exerted by the ligand on vascular SMCs. beta -IL-3-transducing subunit was detected both on cultured SMCs and on endothelial cells and SMCs within atheroma. The analysis of the IL-3-induced biological effects demonstrated that it was able to trigger both mitogenic and motogenic signals. Moreover, we demonstrated that the addition of PD98059, a known inhibitor of the MAP-extracellular signaling-regulated/MAP kinase pathway, completely inhibited IL-3-mediated MAP kinase activation and IL-3-induced migration and proliferation. Finally. IL-3 was found to stimulate vascular endothelial growth factor (VEGF) gene transcription.Conclusions-IL-3, expressed by activated T lymphocytes infiltrating early and advanced atherosclerotic plaques, may sustain the atherosclerotic process either directly, by activating SMC migration and proliferation, or indirectly, via VEGF production.