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Mycophenolic acid inhibits inosine <f>5′</f>-monophosphate dehydrogenase and suppresses production of pro-inflammatory cytokines, nitric oxide, and LDH in macrophages
- Source :
-
Cellular Immunology . Mar2002, Vol. 216 Issue 1/2, p93. 9p. - Publication Year :
- 2002
-
Abstract
- Mycophenolic acid (MPA) inhibits reversibly inosine <f>5′</f>-monophosphate dehydrogenase, an enzyme involved in the de novo synthesis of guanine nucleotides. Previously, mycophenolate mofetil (MMF), the pro-drug of MPA, was shown to exert beneficial effects on the systemic lupus erythematosus (SLE)-like disease in MRLlpr/lpr mice. In this study MPA’s immunomodulating effects in vitro on the murine macrophage cell line IC-21 were investigated. The cells were exposed to MPA together with lipopolysaccharide and IFN-<f>γ</f>. Cytokine, NO2−, and lactate dehydrogenase levels in supernatants and cell lysates were analysed as well as the proliferation of IC-21 cells. MPA exposure reduced the total levels of all molecules investigated and suppressed the proliferation. All MPA-induced effects were reversed by the addition of guanosine to the cultures. Since macrophages play a role in lupus nephritis, our results indicate that modulation of macrophages may be involved in the ameliorating effects of MMF in SLE. [Copyright &y& Elsevier]
- Subjects :
- *IMP dehydrogenase
*G proteins
*SYSTEMIC lupus erythematosus
Subjects
Details
- Language :
- English
- ISSN :
- 00088749
- Volume :
- 216
- Issue :
- 1/2
- Database :
- Academic Search Index
- Journal :
- Cellular Immunology
- Publication Type :
- Academic Journal
- Accession number :
- 8518441
- Full Text :
- https://doi.org/10.1016/S0008-8749(02)00502-6