lnflammation Research Group Division of Immunology, Wellesley Hospital University of Toronto Ontario Toronto M4Y 1J3 Canada.
Mediators Inflamm. 1995;4(1):67-70. doi: 10.1155/S0962935195000123.
Tenidap (TD) was initially defined as a dual inhibitor of cyclooxygenase and lipoxygenase. This study was designed to assess its inhibitory activity against proinflammatory phospholipase A(2). This study shows that TD inhibits the synthesis of pro-inflammatory secretory non-pancreatic phospholipase A(2) (sPLA(2)). Concentrations as low as 0.25 mug/ml (0.725 muM) reduced the release of sPLA(2) by 40% from foetal rat calvarial osteoblasts stimulated with IL-1beta and TNFalpha, whereas a concentration of 2.5 mug/ml (7.25 muM) reduced the release by over 80%. TD also markedly reduced the release of sPLA(2) from unstimulated cells. There was no direct inhibition of sPLA(2) enzymatic activity by TD in vitro. Northern blot analysis showed that TD did not affect the sPLA(2) mRNA levels; however, immunoblotting showed a dose-dependent reduction in sPLA(2) enzyme. These results, together with a marked reduction in sPLA(2) enzymatic activity, suggest that TD inhibits sPLA(2) synthesis at the post-transcriptional level. Therefore TD seems to inhibit the arachidonic acid cascade proximally to cyclooxygenase and lipoxygenase and its anti-inflammatory activity may be related at least in part to the inhibition of sPLA(2) synthesis.
替地达诺（TD）最初被定义为环加氧酶和脂加氧酶的双重抑制剂。本研究旨在评估其对促炎磷脂酶 A2（PLA2）的抑制活性。本研究表明，TD 抑制促炎性分泌型非胰腺磷脂酶 A2（sPLA2）的合成。浓度低至 0.25 μg/ml（0.725 μM）即可使 IL-1β和 TNFα刺激的胎鼠颅骨成骨细胞释放的 sPLA2 减少 40%，而 2.5 μg/ml（7.25 μM）则减少超过 80%。TD 还明显减少了未刺激细胞中 sPLA2 的释放。TD 并未在体外直接抑制 sPLA2 的酶活性。Northern blot 分析表明，TD 不影响 sPLA2 mRNA 水平；然而，免疫印迹显示 sPLA2 酶的剂量依赖性降低。这些结果以及 sPLA2 酶活性的明显降低表明，TD 在转录后水平抑制 sPLA2 的合成。因此，TD 似乎抑制了环加氧酶和脂加氧酶附近的花生四烯酸级联反应，其抗炎活性可能至少部分与抑制 sPLA2 合成有关。
