Delomenie C, Wautier-Pepin M P, Chappey O, Wautier J L
Laboratoire de Biologie Vasculaire et Cellulaire, INSERM U 294, Hôpital Lariboisière, Paris, France.
Exp Cell Res. 1993 Jul;207(1):122-30. doi: 10.1006/excr.1993.1170.
Some cytokines are known to affect both proliferation and activation of cultured human endothelial cells (HEC). We compared the extent of these modifications when induced by several cytokines or by the monocyte-derived endothelial cell inhibitory factor (MECIF) activity. We measured as endothelial activation parameters the expression of endothelium-leukocyte adhesion receptor-1 (ELAM-1, E-selectin), major histocompatibility complex (MHC) class II antigens, interleukin 1 (IL-1), interleukin 6 (IL-6), and prostacyclin. To further investigate if a common or distinct intracellular mechanism was involved in the action of these effectors we studied the influence of indomethacin, a cyclooxygenase inhibitor, on the growth inhibition and the activation effects. Our results showed that IL-1 beta, tumor necrosis factor (TNF)alpha, and MECIF activity induced the expression of ELAM-1 on HEC membrane while transforming growth factor beta (TGF beta), IL-6, and gamma-interferon (IFN-gamma) showed no effect. However, MECIF activity did not induce MHC class II antigens on HEC surface. MECIF activity appeared to be immunologically distinct from IL-1 beta, TNF alpha, and TNF beta (lymphotoxin). IL-6 production by HEC was significantly increased only in the presence of IL-1 beta, TNF alpha, or MECIF activity. Intracellular IL-1 alpha and IL-1 beta levels were markedly enhanced by IL-1 beta and TNF alpha. MECIF activity, TNF alpha, and IL-1 beta significantly increased prostacyclin secretion whereas TGF beta, IL-6, and IFN-gamma showed no significant effect. Indomethacin did not significantly modify ELAM-1 induction and reduced in a nonsignificant manner the antiproliferative effect of MECIF activity, TNF alpha, IL-1 beta, and TGF beta. The effectors studied appeared to modulate differently the expression of endothelial products and activation markers in vitro, suggesting that their effects could be mediated through distinct intracellular pathways. The cyclooxygenase pathway of arachidonic acid metabolism could be involved in the growth inhibitory action of MECIF activity, TNF alpha, IL-1 beta, and TGF beta but an additional putative pathway might also be involved.
已知某些细胞因子会影响培养的人内皮细胞（HEC）的增殖和活化。我们比较了几种细胞因子或单核细胞衍生的内皮细胞抑制因子（MECIF）活性诱导这些修饰的程度。我们将内皮细胞-白细胞粘附受体-1（ELAM-1，E-选择素）、主要组织相容性复合体（MHC）II类抗原、白细胞介素1（IL-1）、白细胞介素6（IL-6）和前列环素的表达作为内皮细胞活化参数进行测量。为了进一步研究这些效应因子的作用是否涉及共同或不同的细胞内机制，我们研究了环氧化酶抑制剂吲哚美辛对生长抑制和活化作用的影响。我们的结果表明，IL-1β、肿瘤坏死因子（TNF）α和MECIF活性可诱导HEC膜上ELAM-1的表达，而转化生长因子β（TGFβ）、IL-6和γ-干扰素（IFN-γ）则无此作用。然而，MECIF活性不会诱导HEC表面的MHC II类抗原。MECIF活性在免疫学上似乎与IL-1β、TNFα和TNFβ（淋巴毒素）不同。仅在存在IL-1β、TNFα或MECIF活性的情况下，HEC产生的IL-6才会显著增加。IL-1β和TNFα可显著提高细胞内IL-1α和IL-1β的水平。MECIF活性、TNFα和IL-1β可显著增加前列环素的分泌，而TGFβ、IL-6和IFN-γ则无显著影响。吲哚美辛不会显著改变ELAM-1的诱导，并且以不显著的方式降低了MECIF活性、TNFα、IL-1β和TGFβ的抗增殖作用。所研究的效应因子在体外似乎对内皮细胞产物和活化标志物的表达有不同的调节作用，这表明它们的作用可能通过不同的细胞内途径介导。花生四烯酸代谢的环氧化酶途径可能参与MECIF活性、TNFα、IL-1β和TGFβ的生长抑制作用，但可能还涉及另一条假定的途径。
