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我们以前证实微管聚合抑制剂Ｃｏｌ（秋水仙碱）可抑制分泌ＴＮＦ—α。本文进一步证实Ｃｏｌ并非干扰将ＴＮＦ—α胞外的分泌过程，因Ｃｏｌ不引起ＴＮＦ—α在细胞内的潴留，而是抑制ＴＮＦ—α的产生。因为：（１）阻断新合成蛋白分泌过程的试剂Ｍｏｎ（莫能菌素），能完全抑制ＴＮＦ—α的释放，将大量ＴＮＦ—α阻留在细胞内。如加用Ｃｏｌ．则Ｍｏｎ阻留于胞内的ＴＮＦ—α明显减少；（２）Ｗｅｓｔｅｒｎｂｌｏｔ显示Ｃｏｌ可抑制ＴＮＦ—α前体一２６ＫＤ蛋白的产生。如在ＬＰｓ刺激的不同时间加Ｃｏｌ，其抑制效应在２～８ｈ内逐渐消失，若同时给予ＬＰＳ与Ｃｏｌ．则Ｃｏｌ的抑制效果最好，说明Ｃｏｌ作用于ＴＮＦ—α生物合成早期。在分子水平上，Ｃｏｌ明显减低ＬＰＳ诱导的ＴＮＦ—αｍＲＮＡ水平。以上资料提示Ｃｏｌ主要通过抑制ＴＮＦ—αｍＲＮＡ转录而减少ＴＮＦ—α的合成。
We have previously demonstrated that microtubule polymerization inhibitor Col (colchicine) inhibits the secretion of TNF-α. This article further confirmed that Col does not interfere with the extracellular secretion of TNF-α, because Col does not cause TNF-α intracellular retention, but inhibits TNF-α production. Because: (1) Mon (monensin), which blocks the process of the new synthetic protein secretion, can completely inhibit the release of TNF-α and block a large amount of TNF-α in the cells. If add Col. (2) Western blot showed that Col inhibited the production of TNF-α precursor-26KD protein. As in the LPs stimulated at different times with Col, its inhibitory effect gradually disappear in 2 ~ 8h, if given both LPS and Col. Col inhibited the best, indicating that Col acts on the early stage of TNF-α biosynthesis. At the molecular level, Col significantly decreased LPS-induced TNF-α mRNA levels. The above data suggest that Col mainly decreases TNF-alpha synthesis by inhibiting TNF-alpha mRNA transcription.