| Summary: | 碩士 === 國防醫學院 === 微生物及免疫學研究所 === 102 === Rheumatoid arthritis (RA) is a systemic, chronic inflammatory disorder that caused by autoimmunity and mediated by inflammatory cytokines. RA primary targets on joints and is characterized by synovial hyperplasia and immune cell infiltration which responsible for produce large quantities of pro-inflammatory cytokines like IL-1and TNF-. These inflammatory cytokines in turn mediate the activation of chondrocytes and synoviocytes to produce matrix metalloproteinases (MMPs) and lead to cartilage destruction. IL-1 and TNF- are also responsible for the induction of cyclooxygenase-2 (COX-2)-PGE2 and inducible nitric oxide synthetase (iNOS)-NO which are known to involve in the pathogenesis of RA.
Quercetin belongs to flavonoids and exists in various foods like red wine, onions, green tea, apple, berries etc. It has been shown to exert antioxidants, anticancer and anti-inflammatory activity. Previous study showed that quercetin preserve activity to inhibit synoviocytes proliferation and block production of MMPs, COX-2 and PGE2. Meanwhile, quercetin also been reported can improves arthritis score via inhibiting cytokines production from macrophage in adjuvant arthritis mouse. However, the effect of quercetin on chondrocytes has not been explored before. Therefore, we aim to examine the potential effect of quercetin in cartilage. Our results demonstrated that quercetin attenuated iNOS expression and restored collagen type II level in TNF-α and IL-1 challenged chondrocytes. Unexpectively, we found quercetin, instead of inhibit, enhanced COX-2 expression on our chondrocytes model. COX-2 and iNOS are known usually positive regulate with each other but their expression were differentially regulated by quercetin . We are currently try to unravel the mechanisms that responsible for this differential effect of quercetin on COX-2 and iNOS. We also observed there are different level of enhancement of COX-2 by quercetin under TNF-α and IL-1β stimulation. Our preliminary results shown quercetin enhances COX-2 expression might via NF-κB activation. In NS-398 and SNP experiment, COX-2 had the little effect on iNOS, and NO did regulate COX-2 expression. In human chondrocytes, there had different results between different cytokines. But generally seen similar results with the porcine chondrocytes.
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