PGE_2与LTB_4在微管对TNF－α合成调节中的作用

The Role of PGE_2 and LTB_4 in The Regulation fo TNF-α Synthesisby Microtubule in The Rat

本研究证实完善的微管功能对ＴＮＦ－α的合成是必要的。如用秋水仙碱（Ｃｏｌ）抑制微管聚合，则可减少ＭΦ产生ＴＮＦ－αＣｏｌ对ＴＮＦ－α的抑制作用部分是由于该药引起前列腺素Ｅ＿２（ＰＧＥ＿２）升高所致，因为用环加氧酶抑制剂消炎痛（Ｉｎｄｏｍ，）阻断ＰＧＥ＿２合成，可部分拮抗Ｃｏｌ的这一抑制作用。此外，Ｃｏｌ可抑制花生四烯酸的另一产物白三烯（ＬＴＢ＿４）的产生，然而补充外源性ＬＴＢ＿４并不影响Ｃｏｌ对ＴＮＦ－α的抑制作用。

Intact microtubule and its normal function have been shown to be necessary for TNF-α pro-duction. TNF-α release by the MΦ was reduced when colchicine(Col.)was used to inhibit its microtubulepolymerization. This suppressive effect of Col.on TNF-α release was found to be partially resulted from theelevated PGE_2 production caused by the drug it self, as shown by the fact that the suppressive effect of Col.could be partially counteracted by blocking of PGE_2 synthesis with indomethacin,a cyclooxygenase inhibitor.Furthermore,Col.was also shown to reduce the release of leukotriene(LTB_4),another metabolite of arachi-donic acid.However,addition of exogenous LTB_4 did not affect the inhibitory effect of Col.on TNF-α pro- duction by the MΦ.