Haddad J J, Land S C, Saadé N E, Safieh-Garabedian B
Oxygen Signaling Group, Tayside Institute of Child Health, Dundee, Scotland, DD1 9SY, United Kingdom.
Biochem Biophys Res Commun. 2000 Aug 2;274(2):500-5. doi: 10.1006/bbrc.2000.3155.
The immunomodulatory potential of thymulin in the perinatal epithelium is not well characterized. In an in vitro model of fetal alveolar type II epithelial cells, we investigated the exhibition of an anti-inflammatory activity of this peptide hormone. Thymulin selectively ameliorated, in a dose-dependent manner, the endotoxin-induced release of IL-1 beta (IC(50) = 657 ng. ml(-1)), but showed no inhibitory effect on IL-6 and TNF-alpha. Zinc, an anti-inflammatory antioxidant, which is required for the biological activity of thymulin, reduced the secretion of IL-1 beta (IC(50) = 62 microM), TNF-alpha (IC(50) = 1000 microM), and, to a lesser extent, IL-6. This cation (100 microM) amplified the effect of thymulin on IL-1 beta and TNF-alpha (IC(50) < 0.1 ng. ml(-1)), but not on IL-6. Analysis of whether thymulin is up-regulating a counterpart anti-inflammatory signaling loop revealed the involvement of an IL-10-sensitive pathway. These results indicate that thymulin acts as a novel dual immunoregulator by enhancing an anti-inflammatory cytoprotective response and depressing an inflammatory signal, an effect synergistically amplified, in part, by cationic zinc.
胸腺生成素在围产期上皮组织中的免疫调节潜力尚未得到充分表征。在胎儿II型肺泡上皮细胞的体外模型中，我们研究了这种肽类激素抗炎活性的表现。胸腺生成素以剂量依赖性方式选择性改善内毒素诱导的IL-1β释放（IC50 = 657 ng·ml-1），但对IL-6和TNF-α无抑制作用。锌是一种抗炎抗氧化剂，是胸腺生成素生物活性所必需的，可减少IL-1β（IC50 = 62 μM）、TNF-α（IC50 = 1000 μM）以及程度较轻的IL-6的分泌。这种阳离子（100 μM）增强了胸腺生成素对IL-1β和TNF-α的作用（IC50 < 0.1 ng·ml-1），但对IL-6无此作用。关于胸腺生成素是否上调相应抗炎信号通路的分析揭示了IL-10敏感途径的参与。这些结果表明，胸腺生成素通过增强抗炎细胞保护反应和抑制炎症信号，作为一种新型的双重免疫调节剂发挥作用，这种作用部分地被阳离子锌协同放大。
