Porreca E, Conti P, Feliciani C, Di Febbo C, Reale M, Mincione G, Neri M, Amerio P, Cuccurullo F
Istituto di Patologia Speciale Medica, Ospedale Civile SS Annunziata, Chieti, Italy.
Atherosclerosis. 1995 Jun;115(2):181-9. doi: 10.1016/0021-9150(94)05510-p.
Vascular cells, including smooth muscle cells (VSMC), may release interleukin 1 (IL-1) and transcribe its genes for both isoforms. Previous studies have shown that cysteinyl-leukotrienes can modulate cytokine production by monocytes and a cytokine-eicosanoid network has been suggested during atherosclerosis. In this study the effects of cysteinyl-leukotriene D4 (LTD4) on IL-1 beta production and IL-1 beta mRNA expression were tested on rat VSMC. LTD4 showed a significant dose-dependent (from basal production of 55 +/- 15 pg/ml to maximal production of 177 +/- 14 pg/ml) and time-dependent (peaking at 24 h 16 +/- 54 pg/ml) increase of IL-1 beta immunoreactivity in the supernatants of conditioned medium and cell lysates. Furthermore, LTD4 induced an increased mRNA expression which began at 1 h and peaked at 12 h incubation time. The production of IL-1 beta was inhibited by MK-571 (from 145 +/- 12 to 60 +/- 10 pg/ml), a specific receptor antagonist of LTD4 and partially reduced by IL-1 receptor antagonist (IL-1 ra) (from 160 +/- 12 to 85 +/- 5 pg/ml). These experiments suggest that cysteinyl-leukotrienes, potentially produced in the vascular wall by leukocytes or by transcellular metabolism, may be involved in local IL-1 production.
包括平滑肌细胞（VSMC）在内的血管细胞可能会释放白细胞介素1（IL-1）并转录其两种亚型的基因。先前的研究表明，半胱氨酰白三烯可以调节单核细胞的细胞因子产生，并且在动脉粥样硬化过程中有人提出了细胞因子-类花生酸网络。在本研究中，检测了半胱氨酰白三烯D4（LTD4）对大鼠VSMC中IL-1β产生和IL-1βmRNA表达的影响。LTD4在条件培养基和细胞裂解物的上清液中显示出IL-1β免疫反应性的显著剂量依赖性增加（从基础产生的55±15 pg/ml增加到最大产生的177±14 pg/ml）和时间依赖性增加（在24小时达到峰值16±54 pg/ml）。此外，LTD4诱导mRNA表达增加，该增加在孵育1小时开始并在12小时达到峰值。MK-571（一种LTD4的特异性受体拮抗剂，从145±12 pg/ml降至60±10 pg/ml）抑制了IL-1β的产生，而IL-1受体拮抗剂（IL-1 ra）则使其部分降低（从160±12 pg/ml降至85±5 pg/ml）。这些实验表明，可能由白细胞或通过跨细胞代谢在血管壁中产生的半胱氨酰白三烯可能参与局部IL-1的产生。
