Resistin stimulates expression of chemokine genes in chondrocytes via combinatorial regulation of c/EBPβ and NF-κB

Ziji Zhang, Zhiqi Zhang, Yan Kang, Changhe Hou, Xin Duan, Puyi Sheng, Linda J. Sandell, Weiming Liao

Research output: Contribution to journalArticle

15 Scopus citations

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-κBco-enhanced the chemokines expression; inhibition of their activity was additive. Thetiming 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.

Original languageEnglish
Pages (from-to)17242-17255
Number of pages14
JournalInternational journal of molecular sciences
Volume15
Issue number10
DOIs
StatePublished - Sep 26 2014

Keywords

  • Chemokines
  • Chondrocytes
  • Resistin
  • Transcription factors

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