Boehm U, Guethlein L, Klamp T, Ozbek K, Schaub A, Fütterer A, Pfeffer K, Howard J C
Institute for Genetics, University of Cologne, Germany.
J Immunol. 1998 Dec 15;161(12):6715-23.
IFN-gamma induces a number of cellular programs functional in innate and adaptive resistance to infectious pathogens. It has recently become clear that the complete cellular response to IFN-gamma is extraordinarily complex, with >500 genes (i.e., approximately 0.5% of the genome) activated. We made suppression-subtractive hybridization differential libraries from IFN-gamma-stimulated primary mouse embryonic fibroblasts and from a mouse macrophage cell line, ANA-1, in each case with reference to unstimulated cells. Of approximately 250 clones sequenced at random from the two libraries, >35% were representatives of one or the other of two small unrelated families of GTPases, the 65-kDa and 47-kDa families. These families dominate the IFN-gamma-induced response in both cell types. We report here the full-length sequences of one new 65-kDa and two new 47-kDa family members. The 65-kDa family members are under transcriptional control of IRF-1, whereas the 47-kDa family members are inducible in embryonic fibroblasts from IRF-1(-/-) mice. Members of both GTPase families are strongly up-regulated in livers of wild-type mice infected with the pathogenic bacterium, Listeria monocytogenes, but not in IFN-gammaR(0/0) mice. These GTPases appear to be dedicated to the IFN-gamma response, since resting levels are negligible and since neither family shows any significant relationship to any other described family of GTPases. Understanding the role of these GTPases in IFN-gamma-mediated resistance against pathogens is the task for the future.
干扰素-γ可诱导多种在先天性和适应性抗感染病原体免疫中发挥作用的细胞程序。最近已明确，细胞对干扰素-γ的完整反应极其复杂，有超过500个基因（即约占基因组的0.5%）被激活。我们分别以未受刺激的细胞为参照，从经干扰素-γ刺激的原代小鼠胚胎成纤维细胞和小鼠巨噬细胞系ANA-1构建了抑制性消减杂交差异文库。从这两个文库中随机测序的约250个克隆中，超过35%是两个不相关的小GTP酶家族（65-kDa和47-kDa家族）中某一个家族的代表。这两个家族在两种细胞类型中主导了干扰素-γ诱导的反应。我们在此报告一个新的65-kDa家族成员和两个新的47-kDa家族成员的全长序列。65-kDa家族成员受IRF-1的转录调控，而47-kDa家族成员在来自IRF-1(-/-)小鼠的胚胎成纤维细胞中可被诱导。在感染致病性细菌单核细胞增生李斯特菌的野生型小鼠肝脏中，这两个GTP酶家族的成员均强烈上调，但在干扰素-γR(0/0)小鼠中则不然。这些GTP酶似乎专门参与干扰素-γ反应，因为其静息水平可忽略不计，且这两个家族与其他已描述的GTP酶家族均无明显关系。了解这些GTP酶在干扰素-γ介导的抗病原体免疫中的作用是未来的任务。
