Porreca E, Di Febbo C, Reale M, Barbacane R, Mezzetti A, Cuccurullo F, Conti P
Cattedra di Patologia Speciale Medica, Universitá di Chieti, Italy.
Atherosclerosis. 1995 Feb;113(1):11-8. doi: 10.1016/0021-9150(94)05413-d.
Recent studies suggest the involvement of inflammatory mechanisms in the progression of atherosclerosis. Cysteinyl leukotrienes and cytokines could orchestrate this progression by acting on the proliferation of vascular smooth muscle cells (VSMC). In cultures of rat VSMC, proliferation was modulated by cysteinyl leukotriene C4 (LTC4) and LTD4, but not LTE4. Co-culturing LTD4 with VSMC produced an increased cell proliferation as assessed by [3H]thymidine incorporation studies (200%) as well as cell counts (70%), using LTD4 at 10(-6)M compared to controls. LTD4 exerted its effect through an interleukin 1 (IL-1)-dependent autocrine regulatory mechanism. When IL-1 was inhibited by using a receptor antagonist (IL-1ra) and a polyclonal antibody to IL-1, we found an inhibition of VSMC proliferation. The increase of VSMC proliferation was associated with the autocrine production of interleukin-1 (IL-1) concomitant to LTD4 stimulation (55.5 +/- 2.5 pg/ml in controls and 177 +/- 0.5 pg/ml in 10(-6)M LTD4). These results may shed new light on the mechanism of inflammatory involvement during atherogenesis, suggesting that the control of cysteinyl leukotrienes may be important in inflammatory processes involving IL-1.
近期研究表明，炎症机制参与动脉粥样硬化的进展。半胱氨酰白三烯和细胞因子可通过作用于血管平滑肌细胞（VSMC）的增殖来调控这一进展。在大鼠VSMC培养物中，半胱氨酰白三烯C4（LTC4）和LTD4可调节增殖，但LTE4无此作用。与VSMC共培养LTD4时，通过[3H]胸腺嘧啶核苷掺入研究（增加200%）以及细胞计数（增加70%）评估发现，与对照组相比，10(-6)M的LTD4可使细胞增殖增加。LTD4通过白细胞介素1（IL-1）依赖性自分泌调节机制发挥作用。当使用受体拮抗剂（IL-1ra）和抗IL-1多克隆抗体抑制IL-1时，我们发现VSMC增殖受到抑制。VSMC增殖的增加与LTD4刺激时自分泌产生的白细胞介素-1（IL-1）有关（对照组为55.5±2.5 pg/ml，10(-6)M LTD4组为177±0.5 pg/ml）。这些结果可能为动脉粥样硬化发生过程中炎症参与机制提供新的线索，表明控制半胱氨酰白三烯在涉及IL-1的炎症过程中可能很重要。
