The SOCS-1 story
The SOCS-1 story
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DOI：
10.1016/s0301-472x(99)00120-4
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发表时间：
1999-12-01
影响因子：
2.6
通讯作者：
Metcalf, D
中科院分区：
文献类型：
--
作者：
Metcalf, D
SOCS-1是一种细胞内蛋白，能够阻断干扰素γ (ifn - γ)或gp130受体调节因子诱导的白血病M1细胞的分化。它的短暂产生很容易被细胞因子刺激诱导，SOCS-1似乎是一个负反馈分子，调节或抑制至少8种细胞因子激活的受体信号。缺乏SOCS-1的小鼠会出现致死性新生儿综合征，包括肝损伤、T淋巴细胞和B淋巴细胞耗竭，以及肝、肺、胰腺、心脏和皮肤的粒细胞-巨噬细胞浸润。在SOCS-1（-/-）小鼠中，这些和相关的血液学异常都可以通过新生儿注射高剂量ifn - γ来模拟。通过注射ipn - γ抗体或将SOCS-1（-/-）小鼠与ifn - γ(-/-)小鼠杂交，可以预防SOCS-1（-/-）小鼠的致命性新生儿疾病，确定ifn - γ是新生儿疾病和死亡的关键。在SOCS-1（-/-）小鼠中，ifn - γ似乎不会过量产生，致命疾病可能是由于-/-细胞对正常水平的ifn - γ的高反应性引起的，通过与ifn - γ(-/-)小鼠杂交而存活到新生儿期的SOCS-1（-/-）小鼠可能最终发展成其他疾病状态，因为SOCS-1的缺失可能使它们对其他细胞因子信号产生高反应。(C) 1999国际实验血液学学会。Elsevier Science Inc.出版。
SOCS-1 is an intracellular protein able to block the differentiation of leukemic M1 cells inducible by interferon gamma (IFN-gamma) or regulators using the gp130 receptor. Its transient production is readily inducible by cytokine stimulation, and SOCS-1 appears to be a negative feedback molecule, modulating or suppressing receptor signaling activated by at least eight cytokines. Mice lacking SOCS-1 develop a lethal neonatal syndrome including liver damage, depletion of T and B lymphocytes, and granulocyte-macrophage infiltration of the liver, lungs, pancreas, heart, and skin. These and the associated hematologic abnormalities in SOCS-1(-/-) mice can all be mimicked by the neonatal injection of high doses of IFN-gamma. The lethal neonatal disease in SOCS-1(-/-) mice is preventable by injection of antibodies to IPN-gamma or by crossing SOCS-1(-/-) mice with IFN-gamma(-/-) mice, identifying IFN-gamma as being essential for the initiation of the neonatal disease and death. IFN-gamma appears not to be overproduced in SOCS-1(-/-) mice, and the lethal disease may arise from hyperresponsiveness of -/- cells to normal levels of IFN-gamma, SOCS-1(-/-) mice allowed to survive the neonatal period by cross-mating with IFN-gamma(-/-) mice may well ultimately develop other disease states, because loss of SOCS-1 potentially renders them hyperresponsive to other cytokine signaling. (C) 1999 International Society for Experimental Hematology. Published by Elsevier Science Inc.