Open AccessDehydroxymethylepoxyquinomicin Inhibits Expression and Production of Inflammatory Mediators in Interleukin-1β-induced Human Chondrocytes
Author(s) -
Venera Cardile,
Giampiero Frasca,
Massimo Libra,
Silvia Caggia,
Kazuo Umezawa,
Annamaria Panico,
Grazia Malaponte
Publication year - 2010
Publication title -
cellular physiology and biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.486
H-Index - 87
eISSN - 1421-9778
pISSN - 1015-8987
DOI - 10.1159/000303058
Subject(s) - chemokine , nitric oxide synthase , microbiology and biotechnology , nitric oxide , interleukin , inflammation , western blot , chemotaxis , cytokine , chemistry , monocyte , immunology , cancer research , biology , biochemistry , gene , receptor , organic chemistry
The present research was carried out to determine the effects of a nuclear factor-kappaB (NF-kappaB) inhibitor, dehydroxymethylepoxyquinomicin (DHMEQ), derivative of the antibiotic epoxyquinomicin C, on normal human chondrocytes treated with interleukin-1beta (IL-1beta). 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-1beta-induced chondrocytes. DHMEQ may become a therapeutic agent for treatment of chondro-degenerative diseases.