| Research Abstract |
The present study investigated roles of heme oxygenase (HO)-1 in rheumatic diseases.
Main results were shown as follows ;
First, weekly administration with an HO-1 inducer, hemin suppresses development of lupus nephritis in MRL/lpr mice by reducing serum anti-DNA antibody level, interferon-γ production, and local expression of iNOS in the kidney. The findings suggest that HO-1 induction therapy is one of promising strategies for lupus nephritis (Takeda Y, Takeno M, et al. Clin Exp Immunol., 2004).
Second, serum HO-1 level is significantly increased in patients with adultonset Still's disease and hemophagocytic syndrome, and that the HO-1 level is closely correlated with disease activity and serum ferritin level, but not cytokines including TNF-α,IL-1,IL-6,IL-8, and IL-18. On the other hand, serum HO-1 level was not elevated in patients having hyperferritinemia due to frequent blood transfusion and liver disorders (Kirino Y, Takeno M et al., Arthritis Research Therapy, 2005). Expression of HO-1 mRNA was not necessarily upregulated in circulating leukocytes from the patients with adult onset Still's disease and hemophagocytic syndrome. Preliminary data indicate that activated macrophages in bone marrow, liver, and lymph nodes may produce HO-1.
Third, HO-1 protein is abundantly expressed in synovial tissues of rheumatoid arthritis. HO-1 expression level in synovial cell lines was inversely correlated with production of proinflammatory cytokines, suggesting the regulatory role of HO-1 in development of inflammation in rheumatoid arthritis. Furthermore, auranofin induces HO-1 expression in synovial cells and the anti-rheumatic pharmacological effects of partly depend on the HO-1 induction (Kobayashi H, Takeno M, et al., Arthritis Rheum, 2006).
|
