Resistin stimulates expression of chemokine genes in chondrocytes via combinatorial regulation of C/EBPβ and NF-κB.
Resistin stimulates expression of chemokine genes in chondrocytes via combinatorial regulation of C/EBPβ and NF-κB.
复制标题
DOI：
10.3390/ijms151017242
复制
发表时间：
2014-09-26
影响因子：
5.6
通讯作者：
Liao W
中科院分区：
文献类型：
--
作者：
Zhang Z;Zhang Z;Kang Y;Hou C;Duan X;Sheng P;Sandell LJ;Liao W
为了进一步研究两种趋化因子基因CCL 3和CCL 4在软骨细胞中响应于Bcln的调节作用，培养了人原代软骨细胞和T/C-28 a2细胞。采用qPCR方法检测细胞内C/EBPβ、NF-κB亚型的表达。用NF-κB抑制剂（IKK-NBD）和C/EBPβ抑制剂（SB 303580）处理C/EBPβ和NF-κ B的时间协同调节，并进行亚细胞定位研究。结果表明，Bcln可以独立地增加趋化因子基因的上调。抵抗素可增加C/EBPβ和NF-κB亚型的表达。C/EBPβ调节基础活性，并随时间稳定增加，直至24小时。NF-κB表达上调，在4 h达高峰。C/EBPβ和NF-κB共同促进趋化因子的表达，其活性抑制是相加的。通过C/EBPβ和c-rel的亚细胞定位证实了软骨细胞中活化的时间。软骨细胞以非限制性的细胞特异性方式与CCRN反应，利用C/EBPβ和NF-κB组合调节趋化因子基因表达。NF-κB活性的瞬时增加增强了C/EBPβ的活性，两种转录因子独立作用于趋化因子基因CCL 3和CCL 4。因此，在软骨细胞中，CCLn通过C/EBPβ和NF-κB的组合调节来刺激CCL 3和CCL 4。
To further investigate the regulation role of two chemokine genes CCL3 and CCL4 in chondrocytes in response to resistin, human primary chondrocytes and T/C-28a2 cells were cultured. The function of resistin on the chemokine genes, and the expression of C/EBPβ, NF-κB isoforms were tested using qPCR. The methods used to investigate timed co-regulation of C/EBPβ and NF-κBwere NF-κB inhibitor (IKK-NBD) and C/EBPβ inhibitor (SB303580) treatments, and subcellular localization, with or without resistin stimulation. Results showed that resistin could increase the up-regulation of chemokine genes independently. Resistin increased the expression of C/EBPβ and NF-κB isoforms. C/EBPβ regulated basal activity and steadily increased over time up to 24h with resistin. NF-κB was up-regulated upon induction with resistin, peaking at 4 h. C/EBPβ and NF-κB co-enhanced the chemokines expression; inhibition of their activity was additive. The timing of activation in chondrocytes was confirmed by subcellular localization of C/EBPβ and c-rel. Chondrocytes react to resistin in a non-restricted cell-specific manner, utilizing C/EBPβ and NF-κB in a combinatorial regulation of chemokine gene expression. The activity of C/EBPβ is augmented by a transient increase in activity of NF-κB, and both transcription factors act independently on the chemokine genes, CCL3 and CCL4. Thus, resistin stimulates CCL3 and CCL4 through combinatorial regulation of C/EBPβ and NF-κB in chondrocytes.
登录
查看更多内容
DOI：
10.4049/jimmunol.0802971
发表时间：
2009-06-01
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Lu YC;Kim I;Lye E;Shen F;Suzuki N;Suzuki S;Gerondakis S;Akira S;Gaffen SL;Yeh WC;Ohashi PS
通讯作者：
Ohashi PS
影响因子：
7
作者：
Sandell, L. J.;Xing, X.;Patra, D.
通讯作者：
Patra, D.
影响因子：
5.8
作者：
Tseng, Pei-Chi;Hsu, Hsing-Chih;Yeh, Sheau-Farn
通讯作者：
Yeh, Sheau-Farn
影响因子：
1
作者：
van der Kraan, Peter M.
通讯作者：
van der Kraan, Peter M.
影响因子：
4.8
作者：
Zhang, Zhiqi;Bryan, Jennifer L.;Sandell, Linda J.
通讯作者：
Sandell, Linda J.