Galizzi J P, Cabrillat H, Rousset F, Ménétrier C, de Vries J E, Banchereau J
UNICET, Laboratory for Immunological Research, Dardilly, France.
J Immunol. 1988 Sep 15;141(6):1982-8.
Human rIL-4 specifically induces the expression of the low affinity receptor for IgE (Fc epsilon R2/CD23) on normal B cells and on the Burkitt lymphoma cell line Jijoye. IL-4 does not induce the generation of the second messenger cAMP in Jijoye cells. PGE2 (at 10(-7) M) was found to inhibit by 50% the IL-4 mediated Fc epsilon R2/CD23 induction on Jijoye cells. The PGE2 half maximum inhibitory concentration (1 nM) was comparable to that inducing a half maximal increase of intracellular cAMP (4nM PGE2). 8-bromo-cAMP (10(-3) M), forskolin (10(-5) M), and cholera toxin (100 ng/ml), which increase intracellular cAMP levels, also inhibited by 40 to 80% the IL-4 induced Fc epsilon R2/CD23 expression on Jijoye cells. PGE2 8-bromo-cAMP, forskolin, and cholera toxin also inhibited the IL-4-induced Fc epsilon R2/CD23 expression on normal B lymphocytes. Taken together these data suggest that PGE2 inhibits the IL-4 induced Fc epsilon R2/CD23 through an increase of intracellular cAMP. In contrast, IFN-gamma, which strongly inhibits IL-4-mediated Fc epsilon R2/CD23 expression on Jijoye cells, did not increase intracellular cAMP levels and thus probably acts through another mechanism. IFN-gamma and PGE2 did not inhibit binding of IL-4 to its receptor. It could be excluded that IFN-gamma and PGE2 were acting via an alteration/desensitization of the IL-4R inasmuch as 24 h pre-incubation of Jijoye cells with these agents affected neither the affinity of 125I-IL-4 for its receptor (Kd = 0.8 to 1.5 x 10(-10) M) nor the maximal number of binding sites per Jijoye cells (Bmax = 390 to 550). Furthermore, IFN-gamma and PGE2 did not affect the internalization and degradation of 125I-IL-4. These data demonstrate that PGE2 and IFN-gamma inhibit the IL-4-mediated induction of Fc epsilon R2/CD23 on B lymphocytes via different mechanisms that do not alter the interaction of IL-4 with its receptor.
人重组白细胞介素-4（rIL-4）特异性诱导正常B细胞和伯基特淋巴瘤细胞系Jijoye上低亲和力IgE受体（FcεR2/CD23）的表达。IL-4不会在Jijoye细胞中诱导第二信使环磷酸腺苷（cAMP）的生成。发现前列腺素E2（PGE2，浓度为10^(-7) M）可抑制Jijoye细胞上IL-4介导的FcεR2/CD23诱导作用达50%。PGE2的半数最大抑制浓度（1 nM）与诱导细胞内cAMP半数最大增加量时的浓度（4 nM PGE2）相当。8-溴-cAMP（10^(-3) M）、福斯可林（10^(-5) M）和霍乱毒素（100 ng/ml）可增加细胞内cAMP水平，它们也使Jijoye细胞上IL-4诱导的FcεR2/CD23表达抑制40%至80%。PGE2、8-溴-cAMP、福斯可林和霍乱毒素也抑制正常B淋巴细胞上IL-4诱导的FcεR2/CD23表达。综合这些数据表明，PGE2通过增加细胞内cAMP来抑制IL-4诱导的FcεR2/CD23表达。相比之下，干扰素-γ（IFN-γ）强烈抑制Jijoye细胞上IL-4介导的FcεR2/CD23表达，但不会增加细胞内cAMP水平，因此可能通过另一种机制起作用。IFN-γ和PGE2不会抑制IL-4与其受体的结合。可以排除IFN-γ和PGE2是通过改变/使IL-4受体脱敏起作用，因为用这些试剂对Jijoye细胞进行24小时预孵育既不影响125I-IL-4与其受体的亲和力（解离常数Kd = 0.8至1.5×10^(-10) M），也不影响每个Jijoye细胞上结合位点的最大数量（最大结合量Bmax = 390至550）。此外，IFN-γ和PGE2不影响125I-IL-4的内化和降解。这些数据表明，PGE2和IFN-γ通过不同机制抑制B淋巴细胞上IL-4介导的FcεR2/CD23诱导作用，且不改变IL-4与其受体的相互作用。
