Stimulation of FcγRI on Primary Sensory Neurons Increases Insulin-Like Growth Factor-I Production, Thereby Reducing Reperfusion-Induced Renal Injury in Mice (Retracted article. See vol. 187, pg. 3448, 2011)
Stimulation of FcγRI on Primary Sensory Neurons Increases Insulin-Like Growth Factor-I Production, Thereby Reducing Reperfusion-Induced Renal Injury in Mice (Retracted article. See vol. 187, pg. 3448, 2011)
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DOI：
10.4049/jimmunol.0902051
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发表时间：
2010-07-15
影响因子：
4.4
通讯作者：
Okajima, Kenji
中科院分区：
文献类型：
--
作者：
Harada, Naoaki;Zhao, Juan;Okajima, Kenji
Fc γ RI对小鼠初级感觉神经元的生物学作用尚未完全了解。感觉神经元刺激增加胰岛素样生长因子-I（IGF-I）的产生，从而减少小鼠缺血/再灌注（I/R）诱导的组织损伤。在这项研究中，我们研究了IgG的Fc片段（IgGFc）是否通过刺激感觉神经元增加IGF-I的产生，从而减少I/R诱导的小鼠肾损伤。IgGFc增加降钙素基因相关肽（CGRP）的释放和细胞cAMP水平从野生型（WT）小鼠分离的背根神经节神经元，而，天然IgG没有。用抗Fc γ RI Ab、蛋白激酶A抑制剂KT 5710和磷脂酶A（2）抑制剂4-溴苯酰溴预处理可抑制IgGFc诱导的这些效应。在WT小鼠中，给予IgGFc增强了肾组织CGRP和IGF-I水平的增加，并减少了I/R诱导的肾损伤。在肾I/R的WT小鼠中，给予IgGFc可抑制caspase-3肾组织水平的增加、中性粒细胞的肾蓄积和肾小管细胞凋亡。用抗IGF-I Ab预处理完全逆转了IgGFc在WT小鼠中诱导的这些作用。天然IgG的给药在经历肾I/R的WT小鼠中未显示任何作用。在CGRP敲除小鼠和去神经WT小鼠中给予IgGFc后，未观察到在WT小鼠中观察到的影响。这些观察结果表明，IgGFc对Fc γ RI的激活可能刺激感觉神经元，从而促进IGF-I的产生，有助于通过减弱小鼠的炎症反应减少再灌注诱导的肾损伤。免疫学杂志，2010，185：1303-1310。
Biological role(s) of Fc gamma RI on mouse primary sensory neurons are not fully understood. Sensory neuron stimulation increases insulin-like growth factor-I (IGF-I) production, thereby reducing ischemia/reperfusion (I/R)-induced tissue injury in mice. In this study, we examined whether the Fc fragment of IgG (IgGFc) increases IGF-I production through sensory neuron stimulation, thereby reducing I/R-induced renal injury in mice. IgGFc increased the calcitonin-gene-related peptide (CGRP) release and cellular cAMP levels in dorsal root ganglion neurons isolated from wild-type (WT) mice, whereas, native IgG did not. Pretreatment with anti-Fc gamma RI Ab, a protein kinase A inhibitor KT5710, and a phospholipase A(2) inhibitor 4-bromophenylacyl bromide inhibited these effects induced by IgGFc. Administration of IgGFc enhanced increases of renal tissue levels of CGRP and IGF-I and reduced I/R-induced renal injury in WT mice. Increases of renal tissue level of caspase-3, renal accumulation of neutorphils, and renal tubular apoptosis were inhibited by administration of IgGFc in WT mice subjected to renal I/R. Pretreatment with anti-IGF-I Ab completely reversed these effects induced by IgGFc in WT mice. Administration of native IgG did not show any effects in WT mice subjected to renal I/R. None of the effects observed in WT mice was seen after IgGFc administration in CGRP-knockout mice and denervated WT mice. These observations suggest that activation of Fc gamma RI by IgGFc may stimulate sensory neurons, thereby promoting IGF-I production, contributing to reduction of the reperfusion-induced renal injury via attenuation of inflammatory responses in mice. The Journal of Immunology, 2010, 185: 1303-1310.