Induction of heme oxygenase-1 inhibits IL-1b nitrite oxide production in articular chondrocytes
- F Rannou1
© The Author(s) 2003
Published: 12 September 2003
IL-1b is one of the main cytokines leading to the degradation of articular cartilage. One mechanism through which this cytokine exerts its effects is by articular chondrocytes being induced to produce nitrite oxide (NO). These findings are supported by clinical studies revealing a significant increase of NO production in the synovial fluid of patients with rheumatoid arthritis and osteoarthritis. Modulating IL-1b-induced NO in articular chondrocytes appears to be an interesting challenge for reducing or inhibiting the cartilage destruction.
Heme oxygenase-1 (HO-1) is an inducible enzyme catalyzing the degradation of heme. The beneficial effects of HO-1 have been described for several diseases. This enzyme confers protection mainly through its antioxidant and anti-inflammatory functions.
The objectives of this work were to investigate the expression and activity of HO-1 in IL-1b-treated articular chondrocytes, and the corresponding molecular mechanism.
We used high-density primary cultures of rabbit articular chondrocytes. HO-1 expression was evaluated by Western blotting. HO-1 activity on IL-1b-induced NO was evaluated with use of the Griess reaction. Transient transfection of and Western blotting for IkBa, NF-κB, inducible nitrite oxide synthase and HO-1 elucidated the molecular mechanism of the HO-1 activity on IL-1b-induced NO.
We found evidence, for the first time, of the inducible expression of HO-1 in articular chondrocytes. Overproduction or overexpression of HO-1 is able to decrease dramatically in a dose-dependent manner the IL-1b-induced NO release in the culture medium from articular chondrocyte culture. The inhibition of NO production occurs at the transcriptional level through an NF-κB-dependent pathway.
These results demonstrate the critical role of HO-1 in inhibiting the IL-1b-induced NO. In vivo experiments are under investigation.