Abstract |
The aim of this study was to evaluate the effects of the immunomodulating drug mycophenolic acid (MPA) on splenocytes in an animal model of systemic lupus erythematosus (SLE), using MRLlpr/lpr mice. MPA reversibly inhibits inosine 5'-monophosphate dehydrogenase, an enzyme involved in the de novo guanosine synthesis. Splenocytes were treated with MPA (at 1 or 10 microM), and stimulated with either lipopolysaccharide (LPS; 10 microg/ml) or concanavalin A (ConA; 1.25 microg/ml). In blocking experiments, guanosine (100 microM) was added to the cultures to inhibit the effects of MPA. Lymphocyte proliferation, enumeration of immunoglobulin producing cells (using ELISPOT) and quantification of anti-double-stranded ( ds) DNA antibodies, IFN-gamma and IL-10 (by ELISA) in supernatants were performed. In addition, cell viability was evaluated using propidium iodide and flow cytometry. We found that MPA-treated splenocytes had dramatically decreased mitogen-induced proliferation and number of immunoglobulin producing cells, down-regulated production of IFN-gamma, IL-10 and IgM anti-dsDNA antibodies. The viability of MPA-treated cells was also decreased. All of the effect modulated by MPA could be neutralized by the addition of guanosine. We conclude that MPA has potent immunomodulating effects on both B and T lymphocytes, modulating not only proliferation, but also the production of cytokines, immunoglobulins and autoantibodies.
|
Authors | C A Jonsson, H Carlsten |
Journal | Clinical and experimental immunology
(Clin Exp Immunol)
Vol. 124
Issue 3
Pg. 486-91
(Jun 2001)
ISSN: 0009-9104 [Print] England |
PMID | 11472413
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
|
Chemical References |
- Adjuvants, Immunologic
- Antibodies, Antinuclear
- Enzyme Inhibitors
- Immunoglobulin M
- Immunoglobulins
- Lipopolysaccharides
- Mitogens
- Concanavalin A
- Guanosine
- Interleukin-10
- Interferon-gamma
- IMP Dehydrogenase
- Mycophenolic Acid
|
Topics |
- Adjuvants, Immunologic
(pharmacology)
- Animals
- Antibodies, Antinuclear
(biosynthesis)
- Cell Division
(drug effects)
- Cells, Cultured
- Concanavalin A
(pharmacology)
- Enzyme Inhibitors
(pharmacology)
- Female
- Guanosine
(pharmacology)
- IMP Dehydrogenase
(antagonists & inhibitors)
- Immunoglobulin M
(metabolism)
- Immunoglobulins
(biosynthesis)
- Interferon-gamma
(biosynthesis)
- Interleukin-10
(biosynthesis)
- Lipopolysaccharides
(pharmacology)
- Lymphocytes
(drug effects, immunology)
- Mice
- Mice, Inbred C57BL
- Mice, Inbred MRL lpr
- Mitogens
(pharmacology)
- Mycophenolic Acid
(pharmacology)
- Spleen
(cytology)
|