Augmentation of ADAMTS9 gene expression by IL‐1β is reversed by NFκB and MAPK inhibitors, but not PI3 kinase inhibitors. (23rd November 2012)

• Record Type: Journal Article
• Authors: Uysal, Sema; Ünal, Zahide Nur; Erdoğan, Serpil; Akyol, Sümeyya; Ramazan Yiğitoğlu, M.; Hirohata, Satoshi; Işık, Bünyamin; Demircan, Kadir
• Is Part Of: Cell biochemistry and function. Volume 31:Number 7(2013:Oct.)
• Page Start: 539
• Page End: 544
• Publication Date: 2012-11-23
• Subjects: Cytochemistry -- Periodicals; Cell metabolism -- Periodicals; Biochemistry -- Periodicals; Cytology -- Periodicals; 572
• DOI: 10.1002/cbf.2932
• Languages: English
• ISSNs: 0263-6484

Abstract

<abstract abstract-type="main"> <title> <x xml:space="preserve">Abstract</x> </title> <p>The pathways involved in the regulation of a disintegrin and metalloproteinase with thrombospondin motifs 9 (ADAMTS9) expression have not yet been elucidated. Therefore, the aim of this study was to investigate the involvement of nuclear factor‐<italic>κ</italic>B (NF‐<italic>κ</italic>B), mitogen activated protein kinases (MAPK) and Phosphatidylinositol 3‐kinase (PI3 kinase) in <italic>ADAMTS9</italic> gene regulation, with special focus on the involvement of NF‐<italic>κ</italic>B in IL‐1<italic>β</italic>‐induced ADAMTS9 expression. The OUMS‐27 chondrosarcoma cells were exposed to IL‐1<italic>β</italic>. They were pretreated with 20 μM PD98059 (specific inhibitor of p44/42 kinase), 10 μM SB203580 (specific inhibitor of p38 kinase), 20 μM SB600125 (MAPK inhibitor), and 1 μM Wortmannin and 10 μM LY294002 (specific inhibitors of PI3 kinase) for 30 min and subsequently incubated with IL‐1<italic>β</italic>. For the effects of NF‐<italic>κ</italic>B and I<italic>κ</italic>B inhibitors, cells were pretreated with curcumin or BAY117085 for 30 min and subsequently incubated with IL‐1<italic>β</italic>. BAY117085 and different concentrations of curcumin were applied to the cells just after the first experiment to determine their concentration effect on <italic>ADAMTS9</italic> gene expression. After total RNA was extracted, they were reversely transcribed with random primers and then real‐time polymerase chain reaction (PCR) was performed on cDNA samples.</p> <p>There was a significant difference between control and stimulated cells in terms of ADAMTS9/<italic>β</italic>‐actin ratio. Wortmannin and LY294002 did not have any repressive effect on the OUMS‐27 whereas SB203580 and SP600125 were found to decrease the expression of <italic>ADAMTS9</italic> gene. BAY 117085 and curcumin, which are two NF‐<italic>κ</italic>B inhibitors, led to a decrease in the ratio of ADAMTS9/<italic>β</italic>‐actin. As a conclusion, the pathways MAPK and NF‐<italic>κ</italic>B were thought to be responsible pathways for the induction of <italic>ADAMTS9</italic> gene. Copyright © 2012 John Wiley & Sons, Ltd.</p> </abstract>