Kohyama T, Takizawa H, Kawasaki S, Akiyama N, Sato M, Ito K, Yamamoto K
Department of Respiratory Medicine, University of Tokyo, School of Medicine, Japan.
Mol Cell Biol Res Commun. 1999 Apr;1(1):72-7. doi: 10.1006/mcbr.1999.0108.
FK506, a potent immunosuppressant, has attracted attention for its potential effectiveness in allergic diseases. Although eosinophils are believed to be one of the important effector cells at the site of allergic inflammation, there have been few reports about the direct effect of FK506 on eosinophils. In the present study, we evaluated if FK506 had any effect on the production of IL-8, one of the important chemokines for a variety of inflammatory cells, from human peripheral eosinophils. Purified eosinophils constitutively released IL-8, which was increased with calcium ionophore (10(-6) M). FK506 showed a dose-dependent suppressive effect on IL-8 production by eosinophils stimulated with calcium ionophore, but showed no effect on unstimulated cells. Evaluation of IL-8 mRNA levels by reverse transcription and polymerase chain reaction demonstrated that FK506 suppressed IL-8 gene expression only in activated eosinophils. FK506 further showed a suppressive effect on eotaxin and MCP-1 release from eosinophils. These findings suggested that FK506 might prevent infiltration of inflammatory cells such as eosinophils by, at least in part, inhibiting chemokine release from eosinophils.
FK506是一种强效免疫抑制剂，因其在过敏性疾病中的潜在疗效而备受关注。尽管嗜酸性粒细胞被认为是过敏性炎症部位重要的效应细胞之一，但关于FK506对嗜酸性粒细胞的直接作用的报道却很少。在本研究中，我们评估了FK506是否对人外周嗜酸性粒细胞产生多种炎症细胞的重要趋化因子之一白细胞介素-8（IL-8）有影响。纯化的嗜酸性粒细胞组成性释放IL-8，钙离子载体（10(-6)M）可使其释放增加。FK506对钙离子载体刺激的嗜酸性粒细胞产生IL-8具有剂量依赖性抑制作用，但对未刺激的细胞无影响。通过逆转录和聚合酶链反应评估IL-8 mRNA水平表明，FK506仅在活化的嗜酸性粒细胞中抑制IL-8基因表达。FK506还对嗜酸性粒细胞释放嗜酸性粒细胞趋化因子和单核细胞趋化蛋白-1具有抑制作用。这些发现表明，FK506可能至少部分通过抑制嗜酸性粒细胞释放趋化因子来阻止嗜酸性粒细胞等炎症细胞的浸润。
