Taylor J L, Turo K A, McCann P P, Grossberg S E
Department of Microbiology, Medical College of Wisconsin, Milwaukee.
J Biol Regul Homeost Agents. 1988 Jan-Mar;2(1):19-24.
Both mouse interferon-beta (MuIFN-beta) and the inhibitor of ornithine decarboxylase (ODC), alpha-difluoromethyl ornithine (DFMO), inhibited the differentiation of mouse 3T3-L1 fibroblasts into adipocytes in a dose-dependent manner. DFMO and MuIFN-beta added together to cultures that were induced to differentiate produced an additive anti-differentiation effect. In contrast to this additive cellular effect, DFMO reduced the antiviral activity of MuIFN-beta in both undifferentiated and differentiated cells; DFMO alone had no detectable effect on replication of encephalomyocarditis virus. Putrescine, the product of ornithine decarboxylation, when added to 3T3-L1 cultures (i) enhanced differentiation, (ii) reversed completely the inhibition of differentiation by DFMO, but (iii) had little effect on the antidifferentiation effect of MuIFN-beta. Polyamine content changed four-fold or less in cultures treated with 0.5 mM DFMO and less than two-fold in cultures treated with 100 IU/ml MuIFN-beta for seven days. Thus, it appears not only that MuIFN-beta and DFMO inhibit differentiation of 3T3-L1 cells by different mechanisms but also that the antiviral action of IFN does not involve the regulation of polyamine metabolism by ornithine decarboxylase.
小鼠干扰素-β（MuIFN-β）和鸟氨酸脱羧酶（ODC）抑制剂α-二氟甲基鸟氨酸（DFMO）均以剂量依赖性方式抑制小鼠3T3-L1成纤维细胞向脂肪细胞的分化。将DFMO和MuIFN-β一起添加到诱导分化的培养物中会产生相加的抗分化作用。与这种相加的细胞效应相反，DFMO在未分化和分化的细胞中均降低了MuIFN-β的抗病毒活性；单独的DFMO对脑心肌炎病毒的复制没有可检测到的影响。鸟氨酸脱羧化产物腐胺添加到3T3-L1培养物中时，（i）增强了分化，（ii）完全逆转了DFMO对分化的抑制作用，但（iii）对MuIFN-β的抗分化作用影响很小。用0.5 mM DFMO处理的培养物中多胺含量变化四倍或更少，用100 IU/ml MuIFN-β处理七天的培养物中多胺含量变化不到两倍。因此，似乎不仅MuIFN-β和DFMO通过不同机制抑制3T3-L1细胞的分化，而且IFN的抗病毒作用不涉及通过鸟氨酸脱羧酶对多胺代谢的调节。
