Reactive oxygen species induce Cox-2 expression via TAK1 activation in synovial fibroblast cells
| Autor: | Yuta Onodera, Takeshi Teramura, Kanae Shigi, Kanji Fukuda, Toshiyuki Takehara |
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| Rok vydání: | 2015 |
| Předmět: |
QH301-705.5
TAK1 SFs synovial fibroblast cells Arthritis RA rheumatoid arthritis Inflammation medicine.disease_cause General Biochemistry Genetics and Molecular Biology Article chemistry.chemical_compound ROS reactive oxygen species In vivo Hyaluronic acid OA model medicine Biology (General) Prostaglandin E2 Fibroblast HA hyaluronic acid chemistry.chemical_classification Reactive oxygen species business.industry medicine.disease PGs prostaglandins Cell biology COX cyclooxygenase medicine.anatomical_structure chemistry Immunology OA osteoarthritis Synovial tissues NAC N-acetyl cysteamine Cox-2 medicine.symptom business Oxidative stress medicine.drug |
| Zdroj: | FEBS Open Bio FEBS Open Bio, Vol 5, Iss 1, Pp 492-501 (2015) |
| ISSN: | 2211-5463 |
| Popis: | Highlights • Oxidative stress in the arthritis joint is involved in generating mediators for inflammation. • Oxidative stress-induced expression of Cox-2 was mediated by MAPKs and NF-κB. • ROS-induced MAPKs and NF-κB were attenuated by inhibition of MAPKKK TAK1. • Inhibition of TAK1 activity resulted in reduced expression of Cox-2 and PGE2. • ROS-induced TAK1 activation and Cox-2 expression was inhibited by antioxidants N-acetyl cysteamine and hyaluronic acid. Oxidative stress within the arthritis joint has been indicated to be involved in generating mediators for tissue degeneration and inflammation. COX-2 is a mediator in inflammatory action, pain and some catabolic reactions in inflamed tissues. Here, we demonstrated a direct relationship between oxidative stress and Cox-2 expression in the bovine synovial fibroblasts. Furthermore, we elucidated a novel mechanism, in which oxidative stress induced phosphorylation of MAPKs and NF-κB through TAK1 activation and resulted in increased Cox-2 and prostaglandin E2 expression. Finally, we demonstrated that ROS-induced Cox-2 expression was inhibited by supplementation of an antioxidant such as N-acetyl cysteamine and hyaluronic acid in vitro and in vivo. From these results, we conclude that oxidative stress is an important factor for generation of Cox-2 in synovial fibroblasts and thus its neutralization may be an effective strategy in palliative therapy for chronic joint diseases. |
| Databáze: | OpenAIRE |
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