Dechanet J, Briolay J, Rissoan M C, Chomarat P, Galizzi J P, Banchereau J, Miossec P
Schering-Plough Laboratory for Immunological Research, Dardilly, France.
J Immunol. 1993 Nov 1;151(9):4908-17.
A major feature of rheumatoid arthritis is an uncontrolled proliferation of synoviocytes. This is consistent with the active production of factors such as platelet-derived growth factor (PDGF) and IL-1 by the synovitis, which act in vivo as well as in vitro as potent synoviocyte growth factors. We have previously shown that IL-4 is able to inhibit growth factor production in an ex vivo model of synovitis. Herein, we show that IL-4 strongly inhibited PDGF and IL-1 beta stimulated rheumatoid arthritis synoviocyte proliferation in a dose-dependent manner and through its 130 kDa receptor. This antiproliferative effect of IL-4 directly correlated with a blockade of the synoviocyte cell cycle at the G0 + G1 phases. We also observed that IL-4 induced striking morphologic changes in IL-1 beta or PDGF-stimulated synoviocytes, including increased volume and granulosity. These changes led to major perturbations of the cell monolayer, associated with a marked decrease of synoviocyte viability. Taken together, these data indicate that IL-4 inhibits growth factor-induced proliferation of synoviocytes by interfering with the cell cycle, and by decreasing cell survival.
类风湿性关节炎的一个主要特征是滑膜细胞不受控制地增殖。这与滑膜炎活跃产生血小板衍生生长因子（PDGF）和白细胞介素-1（IL-1）等因子一致，这些因子在体内和体外均作为强大的滑膜细胞生长因子发挥作用。我们之前已经表明，白细胞介素-4（IL-4）能够在滑膜炎的体外模型中抑制生长因子的产生。在此，我们表明IL-4通过其130 kDa受体以剂量依赖的方式强烈抑制PDGF和IL-1β刺激的类风湿性关节炎滑膜细胞增殖。IL-4的这种抗增殖作用与滑膜细胞在G0 + G1期的细胞周期阻滞直接相关。我们还观察到，IL-4在IL-1β或PDGF刺激的滑膜细胞中诱导了显著的形态学变化，包括体积和颗粒度增加。这些变化导致细胞单层出现重大紊乱，并伴有滑膜细胞活力的显著下降。综上所述，这些数据表明IL-4通过干扰细胞周期和降低细胞存活率来抑制生长因子诱导的滑膜细胞增殖。
