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- Title
Denbinobin upregulates miR-146a expression and attenuates IL-1β-induced upregulation of ICAM-1 and VCAM-1 expressions in osteoarthritis fibroblast-like synoviocytes.
- Authors
Yang, Chia-Ron; Shih, Kao-Shang; Liou, Jing-Ping; Wu, Yi-Wen; Hsieh, I-Ni; Lee, Hsueh-Yun; Lin, Tzu-Cheng; Wang, Jyh-Horng
- Abstract
Interleukin-1β (IL-1β) upregulates intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) expressions in osteoarthritis fibroblast-like synoviocytes (OA-FLS) via nuclear factor (NF)-κB-mediated mechanism; enhancement of leukocyte infiltration and upregulation of proinflammatory mediators play a crucial role in OA pathophysiology. MicroRNA (miR)-146a suppresses inflammatory responses by inhibiting NF-κB activity and target gene expression, and epigenetic mechanisms are reportedly involved in miR expression regulation. Here, we aimed to verify the inhibition of ICAM-1/VCAM-1 expression in OA-FLS on denbinobin treatment and to determine whether this inhibition was due to the miR-146a-dependent pathway. We also assessed the epigenetic regulation caused by histone acetyltransferases involved in denbinobin action. Denbinobin attenuated the upregulation of IL-1β-induced ICAM-1/VCAM-1 expression and monocyte adhesion to OA-FLS. The mechanism underlying the inhibitory effects of denbinobin involved miR-146a induction, which in turn inhibited NF-κB signaling. This is because miR-146a inhibitor abrogated the inhibitory effects of denbinobin. Furthermore, histone acetyltransferase inhibitor attenuated the denbinobin-induced upregulation of miR-146a expression and inhibited the acetylation of NF-κB-binding sites located within the miR-146a promoter region. These data suggest that an epigenetic mechanism plays a crucial role in the upregulation of miR-146a expression in response to denbinobin treatment. Our overall findings suggest that denbinobin can be used as a potent anti-inflammatory agent. Key message: • Denbinobin inhibited IL-1β-induced ICAM-1/VCAM-1 expression and monocyte adhesion to OA-FLS. • It was due to denbinobin increased miR-146a level, which in turn inhibited NF-κB signaling. • Our overall findings suggest that denbinobin can be used as a potent anti-inflammatory agent.
- Subjects
OSTEOARTHRITIS; FIBROBLASTS; INTERLEUKIN-1; MICRORNA; ACETYLTRANSFERASES
- Publication
Journal of Molecular Medicine, 2014, Vol 92, Issue 11, p1147
- ISSN
0946-2716
- Publication type
Article
- DOI
10.1007/s00109-014-1192-8