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Int. J. Mol. Sci. 2014, 15(10), 17242-17255;

Resistin Stimulates Expression of Chemokine Genes in Chondrocytes via Combinatorial Regulation of C/EBPβ and NF-κB

Department of Orthopaedic Surgery, the First Affiliated Hospital of Sun Yat-sen University, Guangzhou 510080, China
Department of Orthopaedic Surgery, Washington University School of Medicine at Barnes-Jewish Hospital, St. Louis, MO 63110, USA
These authors contributed equally to this work.
Authors to whom correspondence should be addressed.
Received: 12 July 2014 / Revised: 2 September 2014 / Accepted: 19 September 2014 / Published: 26 September 2014
(This article belongs to the Section Biochemistry)
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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-κB were 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. View Full-Text
Keywords: resistin; chondrocytes; chemokines; transcription factors resistin; chondrocytes; chemokines; transcription factors

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Zhang, Z.; Zhang, Z.; Kang, Y.; Hou, C.; Duan, X.; Sheng, P.; Sandell, L.J.; Liao, W. Resistin Stimulates Expression of Chemokine Genes in Chondrocytes via Combinatorial Regulation of C/EBPβ and NF-κB. Int. J. Mol. Sci. 2014, 15, 17242-17255.

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