Dehydroxymethylepoxyquinomicin Inhibits Expression and Production of Inflammatory Mediators in Interleukin-1β-induced Human Chondrocytes

Cellular Physiology and Biochemistry

关键词: Anti-inflammatory effects;    Cartilage;    Chemokines;    Cyclooxygenase;    DHMEQ;    Nitric oxide;   

DOI  :  10.1159/000303058

学科分类：分子生物学，细胞生物学和基因

来源: S Karger AG

【 摘 要 】

The present research was carried out to determine the effects of a nuclear factor-kappaB (NF-ĸB) inhibitor, dehydroxymethylepoxyquinomicin (DHMEQ), derivative of the antibiotic epoxyquinomicin C, on normal human chondrocytes treated with interleukin-1β (IL-1β). This is a cell model particularly useful to reproduce the mechanisms involved in degenerative arthropathies, where oxidative-inflammatory stress determines a progressive destruction of the articular cartilaginous tissue. The expression of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), and inter-cellular adhesion molecule (ICAM)-1 was evaluated through Western blot analysis. The release of chemokines like monocyte chemoattractant protein-1 (MCP-1), regulated upon normal activation T-cell expressed and secreted (RANTES), and interleukin-8 (IL-8) were determined by ELISA assays. DHMEQ acts as a potent inhibitor of iNOS and COX-2 gene expression while also suppressing the production of nitrite in human chondrocytes. In addition, DHMEQ induces a significant dose-dependent decrease in ICAM expression, MCP-1, RANTES, and IL-8 release. DHMEQ helps to decrease the expression and production of pro-inflammatory mediators in IL-1β-induced chondrocytes. DHMEQ may become a therapeutic agent for treatment of chondro-degenerative diseases.

【 授权许可】

CC BY-NC-ND