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MR Vol.11 No.1 indexに戻る
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MODERN RHEUMATOLOGY
Vol.11 No.1 |
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Mizoribine, an inhibitor of inosine monophosphate
dehydrogenase, inhibits interleukin-6 production by freshly prepared
rheumatoid synovial cells |
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| E. Sugiyama1, M. Ikemoto1, H. Taki1, M.
Maruyama1, N. Yamashita1, M. Kobayashi1 |
| (1)First Department of Internal Medicine, Toyama
Medical and Pharmaceutical University, 2630 Sugitani, Toyama 930-0194,
Japan |
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| Abstract |
| Abstract Mizoribine, an immunosuppressive drug,
has been used for treatment in organ transplantation, lupus nephritis,
and rheumatoid arthritis (RA). On the basis of in vitro experiments,
mizoribine has been postulated to be an inhibitor of inosine monophosphate
(IMP) dehydrogenase, a pivotal enzyme in the formation of guanine
ribonucleotides from IMP. To further characterize the mechanism of
the antirheumatic action of this drug, we examined the effect of
mizoribine on the production of interleukin (IL)-6, a major inflammatory
cytokine in rheumatoid synovia, by freshly prepared rheumatoid synovial
cells (RSC). Mizoribine (1.25-5 7g/ml) was able to inhibit the spontaneous
production of IL-6 by fresh RSC in a dose-response fashion. The addition
of guanosine monophosphate (GMP) reversed its inhibitory effects.
In addition, mizoribine inhibited the enhanced production of IL-6
by the IL-1! and/or tumor necrosis factor !-stimulated RSC. Inhibition
was also observed at the mRNA level, determined by Northern blot
analysis. In contrast, mizoribine did not affect IL-8 production
by these cells. These data suggest that mizoribine inhibits IL-6
production by fresh RSC, possibly owing to the depletion of intracellular
GMP, and that this inhibitory effect of the drug on rheumatoid synovial
cells may be related to its efficacy in RA. |
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| Key words |
| Key words Guanosine triphosphate (GTP) ・ Interleukin-6
・ mizoribine ・ Rheumatoid arthritis ・ Synovial cells |
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