Ho C K, Wang S Y, Ou B R, Shiao M S, Chen H Y, Kuwata T
Department of Medical Research, Veterans General Hospital, Taiwan, Republic of China.
Differentiation. 1989 Mar;40(1):70-5. doi: 10.1111/j.1432-0436.1989.tb00815.x.
The effect of retinoic acid (RA) on the level of interferon (IFN)-induced 2-5 oligoadenylate (2-5A) synthetase activity was examined in human histiocytic lymphoma U937 cells and WISH cells** in order to ascertain the role of this polymerase in interaction between IFNs and RA. Cultures containing both IFNs (1-100 U/ml) and RA (0.1-10 microM) consistently had higher levels of enzyme activity than corresponding cells treated with IFN alone and this was true for all three types of IFNs in both cell lines. The potentiating effect of RA was dose- and time-dependent and under optimal conditions, the induction of the synthetase was synergistic between IFN-beta (10-100 U/ml) and RA (0.1-10 microM). Furthermore, pretreatment (but not posttreatment) with RA followed by subsequent treatment with IFNs preferentially induced higher levels of enzyme activity in U937 cells but not in WISH cells. In addition, our results indicated that the modulating effect of RA on IFNs did not involve interaction at the receptor level and the level of enhancement of 2-5A synthetase activity was not in parallel with either cell-growth arrest or promotion of differentiation. Lastly, the present study raises the possibility that interactions between IFNs and RA, in either a synergistic or antagonistic manner, may be mediated through amplification of the 2-5A system.
为了确定这种聚合酶在干扰素（IFN）与视黄酸（RA）相互作用中的作用，研究了视黄酸（RA）对人组织细胞淋巴瘤U937细胞和WISH细胞中IFN诱导的2-5寡腺苷酸（2-5A）合成酶活性水平的影响。同时含有IFN（1-100 U/ml）和RA（0.1-10 microM）的培养物中的酶活性水平始终高于仅用IFN处理的相应细胞，两种细胞系中的所有三种类型的IFN都是如此。RA的增强作用具有剂量和时间依赖性，在最佳条件下，IFN-β（10-100 U/ml）和RA（0.1-10 microM）之间对合成酶的诱导是协同的。此外，先用RA预处理（而非后处理），随后用IFN处理，优先在U937细胞中诱导出更高水平的酶活性，但在WISH细胞中则不然。另外，我们的结果表明，RA对IFN的调节作用不涉及受体水平的相互作用，并且2-5A合成酶活性的增强水平与细胞生长停滞或分化促进均不平行。最后，本研究提出了一种可能性，即IFN与RA之间以协同或拮抗方式的相互作用可能是通过2-5A系统的放大来介导的。
