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Int. J. Mol. Sci. 2014, 15(10), 17242-17255; doi:10.3390/ijms151017242

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

1
Department of Orthopaedic Surgery, the First Affiliated Hospital of Sun Yat-sen University, Guangzhou 510080, China
2
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, Molecular and Cellular Biology)
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Abstract

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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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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MDPI and ACS Style

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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