Sidell N, Taga T, Hirano T, Kishimoto T, Saxon A
Department of Pathology, UCLA School of Medicine 90024.
J Immunol. 1991 Jun 1;146(11):3809-14.
In this report we demonstrate that retinoic acid (RA) down-regulated the number of IL-6R on human leukocyte cell lines, including the myeloma cell line AF10, and two B cell hybridomas that correspond to cells at earlier stages of B cell development. Using AF10 cells, whose growth was determined to be mediated by the autocrine action of IL-6, we found that RA reduction of IL-6R was concentration-dependent over a range of 10(-11) to 10(-5) M and corresponded to the ability of the retinoid to inhibit cell proliferation. The down-regulation of IL-6R number by RA was accompanied by reduced IL-6R mRNA expression. RA did not affect endogeneous IL-6 synthesis or secretion from AF10 cells. However, addition of exogenous rIL-6 could overcome RA-induced growth inhibition. Menthol, a structurally unrelated compound to RA, also suppressed IL-6R expression and, correspondingly, inhibited cell growth. Taken together, our results suggest that the antiproliferative action of RA on AF10 cells is caused by reduction of IL-6R expression and subsequent inhibition of IL-6-mediated autocrine growth. These findings suggest the possibility that down-regulation of IL-6R is a means by which RA can modulate immune function.
在本报告中，我们证明视黄酸（RA）可下调人白细胞细胞系上白细胞介素-6受体（IL-6R）的数量，这些细胞系包括骨髓瘤细胞系AF10以及两个与B细胞发育早期阶段相对应的B细胞杂交瘤。利用生长被确定为由IL-6自分泌作用介导的AF10细胞，我们发现RA对IL-6R的减少在10^(-11)至10^(-5) M范围内呈浓度依赖性，且与类视黄醇抑制细胞增殖的能力相对应。RA对IL-6R数量的下调伴随着IL-6R mRNA表达的降低。RA不影响AF10细胞内源性IL-6的合成或分泌。然而，添加外源性重组人IL-6（rIL-6）可克服RA诱导的生长抑制。薄荷醇是一种与RA结构不相关的化合物，也可抑制IL-6R表达，并相应地抑制细胞生长。综上所述，我们的结果表明RA对AF10细胞的抗增殖作用是由IL-6R表达的降低以及随后对IL-6介导的自分泌生长的抑制所引起的。这些发现提示IL-6R下调可能是RA调节免疫功能的一种方式。
