Suppression of Erosive Arthritis by NF-κB Inhibitors

Excess activation of NF-kappa B is often involved in inflammation and cancer progression. We have developed a specific NF-kappa B inhibitor dehydroxyepoxyquinomicin (DHMEQ). It binds to the specific cysteine residue of Rel family proteins. DHMEQ inhibited cytokine secretions and osteoclastogenesis in cultured macrophages. It inhibited various animal models of inflammation and cancer. Especially, it inhibited type 2-induced rheumatoid arthritis without any toxicity in mice. It also decreased the number of osteoclasts in the inflammatory tissues. Thus, excess activation of NF-kappa B is essential for rheumatoid arthritis, and DHMEQ is a candidate of new anti-rheumatoid chemotherapeutic agent.