Impairment of cellular immunity is associated with overexpression of heat shock protein 70 in neonatal pigs with intrauterine growth retardation
Impairment of cellular immunity is associated with overexpression of heat shock protein 70 in neonatal pigs with intrauterine growth retardation
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DOI：
10.1007/s12192-012-0326-6
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发表时间：
2012-01
影响因子：
3.8
通讯作者：
X. Zhong;Wei Li;Xuexin Huang;Lili Zhang;Mireguli Yimamu;Nasir Raiput;Yanmin Zhou;Tian Wang
中科院分区：
文献类型：
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作者：
X. Zhong;Wei Li;Xuexin Huang;Lili Zhang;Mireguli Yimamu;Nasir Raiput;Yanmin Zhou;Tian Wang
胎儿宫内发育迟缓（IUGR）的新生儿容易受到细胞免疫功能下降。近年来，越来越多的证据表明，热休克蛋白70可能作为一种危险信号，对先天免疫系统和促进受体介导的细胞凋亡。以IUGR新生仔猪为研究对象，检测了仔猪免疫功能及肠道热休克蛋白70（Hsp 70）、核因子-κ B（NF-κB）和叉头盒O3 a（FoxO 3a）的表达。在出生后第7天采集正常体重（NBW）仔猪和IUGR仔猪的血液、十二指肠、空肠和回肠样品。此外，为了测试Hsp 70是否与NF-κB和FoxO 3a的调节相关，在IEC-6细胞中使用小RNA干扰（siRNA）沉默Hsp 70。IUGR仔猪体重和肠重显著低于NBW仔猪（p < 0.05）。IUGR仔猪外周血淋巴细胞增殖能力显著降低（p < 0.05）。IUGR仔猪血清中细胞因子（IFN-γ、IL-4、IL-10、IL-1和IL-8）浓度较低。IUGR仔猪回肠中IFN-γ和IL-10水平降低（p < 0.05），IL-4水平升高（p < 0.05）。IUGR仔猪Hsp 70和FoxO 3a表达增加，NF-κB活性降低（p < 0.05）。此外，siRNA介导的Hsp 70下调可增加NF-κB活性，抑制FoxO 3a表达，减少细胞凋亡。相反，Hsp 70的过表达抑制NF-κB活化。总之，IUGR损害新生猪的免疫功能。IUGR仔猪免疫力低下与Hsp 70过表达有关，Hsp 70过表达损害NF-κB信号传导并上调FoxO 3a表达。
Neonates with intrauterine growth retardation (IUGR) are susceptible to decreases in cellular immunity. In recent years, a growing body of evidence indicates that Hsp70 may serve as a danger signal to the innate immune system and promote receptor-mediated apoptosis. Using neonatal pigs with IUGR, we investigated immune function of pigs and expression of heat shock protein 70 (Hsp70), nuclear factor-kappa B (NF-κB), and forkhead box O 3a (FoxO3a) in the intestinal tract. Samples from the blood, duodenum, jejunum, and ileum of normal body weight (NBW) piglets and IUGR piglets were collected at day 7 after birth. Furthermore, to test whether Hsp70 is associated with regulation of NF-κB and FoxO3a, Hsp70 was silenced using small RNA interference (siRNA) in IEC-6 cells. Body and intestinal weights were lower in IUGR piglets than in NBW piglets (p < 0.05). Proliferation of peripheral blood lymphocytes was decreased (p < 0.05) in IUGR piglets. Cytokine concentrations (IFN-γ, IL-4, IL-10, IL-1, and IL-8) were lower in serum of IUGR piglets. The levels of IFN-γ and IL-10 were decreased (p < 0.05) in the ileum of IUGR piglets, but IL-4 was increased (p < 0.05). The expressions of Hsp70 and FoxO3a were increased, and NF-κB activity was downregulated in IUGR piglets (p < 0.05). Furthermore, siRNA-mediated Hsp70 downregulation increased NF-κB activity, inhibited expression of FoxO3a, and decreased cell apoptosis. In contrast, overexpression of Hsp70 inhibited NF-κB activation. In conclusion, IUGR impairs immune functions in neonatal pigs. An inefficient immunity in IUGR piglets is associated with overexpression of Hsp70, which impairs NF-κB signaling and upregulates FoxO3a expression.