Interleukin-1 induced nuclear factor-B binds to a disintegrin-like and metalloproteinase with thrombospondin type 1 motif 9 promoter in human chondrosarcoma cells


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Altuntas A., OSKAY HALAÇLI S., Cakmak O., Erden G., Akyol S., Ugurcu V., ...Daha Fazla

MOLECULAR MEDICINE REPORTS, cilt.12, ss.595-600, 2015 (SCI İndekslerine Giren Dergi) identifier identifier identifier

  • Cilt numarası: 12 Konu: 1
  • Basım Tarihi: 2015
  • Doi Numarası: 10.3892/mmr.2015.3444
  • Dergi Adı: MOLECULAR MEDICINE REPORTS
  • Sayfa Sayıları: ss.595-600

Özet

Nuclear factor-B (NF-B) is involved in the regulation of inflammation-associated genes. NF-B forms dimers which bind with sequences referred to as NF-B 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-B within its promoter region. Interleukin-1 (IL-1) affects cartilage metabolism and is involved in the NF-B pathway. It is therefore hypothesized that NF-B binding with ADAMTS9 promoters may activate IL-1, thereby promoting chondrocytic cell growth. In the present study, the OUMS-27 chondrocytic human chondrosarcoma cell line was treated with IL-1 with or without inhibitors of NF-B signaling pathways. Chromatin immunoprecipitation (ChIP) and electromobility shift assays (EMSA) were conducted order to analyze the binding of NF-B with the ADAMTS9 promoter region. NF-B-p65 subunit phosphorylation was promoted in IL-1-treated cells, which were not treated with inhibitors of NF-B signaling pathways. By contrast, NF-B-p65 subunit phosphorylation was inhibited in cells that had been treated with BAY-117085, an NF-B pathway inhibitor. ChIP and EMSA assays demonstrated that, following treatment with IL-1, NF-B-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-B may be involved in IL-1-induced activation of ADAMTS9 in human chondrocytes.