Interleukin-1β induced nuclear factor-κB binds toa disintegrin-like and metalloproteinase with thrombospondin type 1 motif 9 promoter in human chondrosarcoma cells

Aynur Altuntas, Sevil Oskay Halacli, Ozlem Cakmak, Gonul Erden, Sumeyya Akyol, Veli Ugurcu, Satoshi Hirohata, Kadir Demircan

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

Nuclear factor-κB (NF-κB) is involved in the regulation of inflammation-associated genes. NF-κB forms dimers which bind with sequences referred to as NF-κB sites (9-11 bp). A disintegrin-like and metalloproteinase with thrombospondin type 1 motif 9 (ADAMTS9) is a type of proteoglycanase, which proteolytically cleaves versican and aggrecan. ADAMTS9 is a cytokine-inducible gene that contains binding sites for NF-κB within its promoter region. Interleukin-1β (IL-1β) affects cartilage metabolism and is involved in the NF-κB pathway. It is therefore hypothesized that NF-κB binding with ADAMTS9 promoters may activate IL-1β, thereby promoting chondrocytic cell growth. In the present study, the OUMS-27 chondrocytic human chondrosarcoma cell line was treated with IL-1β with or without inhibitors of NF-κB signaling pathways. Chromatin immunoprecipitation (ChIP) and electromobility shift assays (EMSA) were conducted order to analyze the binding of NF-κB with the ADAMTS9 promoter region. NF-κB-p65 subunit phosphorylation was promoted in IL-1β-treated cells, which were not treated with inhibitors of NF-κB signaling pathways. By contrast, NF-κB-p65 subunit phosphorylation was inhibited in cells that had been treated with BAY-117085, an NF-κB pathway inhibitor. ChIP and EMSA assays demonstrated that, following treatment with IL-1β, NF-κB-p65 bound to elements located at -1177 and -1335 in the ADAMTS9 promoter region, in contrast to the untreated samples. The results of the present study suggested that NF-κB may be involved in IL-1β-induced activation of ADAMTS9 in human chondrocytes.

Original languageEnglish
Pages (from-to)595-600
Number of pages6
JournalMolecular Medicine Reports
Volume12
Issue number1
DOIs
Publication statusPublished - Jul 1 2015

Keywords

  • A disintegrin-like and metalloproteinase with thrombospondin type 1 motif 9
  • Interleukin-1β
  • Nuclear factor-κB

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Genetics
  • Oncology
  • Cancer Research

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