Park Jiyoung, Kim Mijin, Na Giyoun, Jeon Iksoo, Kwon Yong-kuk, Kim Jae-hong, Youn Hyesook, Koo Yongbum
School of Biotechnology and Biomedical Science, Inje University, Gimhae 621-749, South Korea.
Mol Cell Endocrinol. 2007 Nov 15;278(1-2):7-17. doi: 10.1016/j.mce.2007.08.002. Epub 2007 Aug 10.
FK506-binding protein 51(FKBP51, coded by FKBP5) is a co-chaperone molecule that interacts with the chaperone HSP90 and the glucocorticoid receptor (GR) in an inactive GR complex. It is a negative regulator of glucocorticoid action and is replaced by the positive regulator, FK506-binding protein 52 (FKBP52, coded by FKBP4) when hormone binds to GR, which renders the GR complex active. In this study, we found that the expression of FKBP51 mRNA in 12 organs of Newcastle disease virus (NDV)-infected chickens was robustly induced. The level of corticosterone in NDV-infected chickens was also elevated, approximately 2- to 6.5-fold in the organs compared to non-infected control chickens. The induction of FKBP51 mRNA expression was reproduced by dexamethasone treatment, indicating a role for glucocorticoids in the systemic induction of FKBP51 mRNA expression. In chicken UMNSAH/DF-1 cells, nuclear factor kappaB (NF-kappaB) was activated in an FKBP51-dependent manner. Regulation of the three NF-kappaB-dependent, anti-apoptotic genes, bcl-2, bcl-x and bfl-1/A1 was investigated in UMNSAH/DF-1 cells. Dexamethasone treatment of UMNSAH/DF-1 cells resulted in up-regulation of bcl-2, and down-regulation of bcl-x and bfl-1/A1. Expression of FKBP51 also resulted in down-regulation of bfl-1/A1, but had no effect on bcl-2 and bcl-x, suggesting the involvement of glucocorticoid-FKBP51-NF-kappaB signaling in the regulation of expression of bfl-1/A1 in UMNSAH/DF-1 cells. We observed organ-specific up- or down-regulation of expression of, bcl-2, bcl-x and bfl-1/A1 in NDV-infected and dexamethasone-treated chickens. Differential regulation of bfl-1/A1, bcl-2 and bcl-x upon NDV-infection and dexamethasone treatment suggests that additional factors are involved in the regulation of these genes. These results suggest that systemic elevation of FKBP51 in NDV-infected chickens activates NF-kappaB, which cooperates with other factors to regulate the expression of NF-kappaB-dependent genes.
FK506结合蛋白51（FKBP51，由FKBP5编码）是一种共伴侣分子，它在无活性的糖皮质激素受体（GR）复合物中与伴侣蛋白HSP90和糖皮质激素受体相互作用。它是糖皮质激素作用的负调节因子，当激素与GR结合时，它会被正调节因子FK506结合蛋白52（FKBP52，由FKBP4编码）取代，从而使GR复合物激活。在本研究中，我们发现新城疫病毒（NDV）感染鸡的12个器官中FKBP51 mRNA的表达被强烈诱导。NDV感染鸡的皮质酮水平也升高，与未感染的对照鸡相比，器官中的皮质酮水平大约升高了2至6.5倍。地塞米松处理可重现FKBP51 mRNA表达的诱导，表明糖皮质激素在FKBP51 mRNA表达的全身诱导中起作用。在鸡UMNSAH/DF-1细胞中，核因子κB（NF-κB）以FKBP51依赖的方式被激活。在UMNSAH/DF-1细胞中研究了三个NF-κB依赖的抗凋亡基因bcl-2、bcl-x和bfl-1/A1的调控。地塞米松处理UMNSAH/DF-1细胞导致bcl-2上调，bcl-x和bfl-1/A1下调。FKBP51的表达也导致bfl-1/A1下调，但对bcl-2和bcl-x没有影响，这表明糖皮质激素-FKBP51-NF-κB信号通路参与了UMNSAH/DF-1细胞中bfl-1/A1表达的调控。我们观察到NDV感染和地塞米松处理的鸡中bcl-2、bcl-x和bfl-1/A1表达的器官特异性上调或下调。NDV感染和地塞米松处理后bfl-1/A1、bcl-2和bcl-x的差异调节表明，这些基因的调控涉及其他因素。这些结果表明，NDV感染鸡中FKBP51的全身升高激活了NF-κB，NF-κB与其他因素协同调节NF-κB依赖基因的表达。
