دورية أكاديمية
Attenuation of murine lupus nephritis by mycophenolate mofetil.
| العنوان: | Attenuation of murine lupus nephritis by mycophenolate mofetil. |
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| المؤلفون: | Van Bruggen MC; Division of Nephrology, University Hospital St. Radboud, Nijmegen, The Netherlands., Walgreen B, Rijke TP, Berden JH |
| المصدر: | Journal of the American Society of Nephrology : JASN [J Am Soc Nephrol] 1998 Aug; Vol. 9 (8), pp. 1407-15. |
| نوع المنشور: | Journal Article; Research Support, Non-U.S. Gov't |
| اللغة: | English |
| بيانات الدورية: | Publisher: Wolters Kluwer Health, on behalf of the American Society of Nephrology Country of Publication: United States NLM ID: 9013836 Publication Model: Print Cited Medium: Print ISSN: 1046-6673 (Print) Linking ISSN: 10466673 NLM ISO Abbreviation: J Am Soc Nephrol Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: 2023- : Hagerstown, MD : Wolters Kluwer Health, on behalf of the American Society of Nephrology Original Publication: Baltimore, MD : Williams & Wilkins, c1990- |
| مواضيع طبية MeSH: | Immunosuppressive Agents/*pharmacology , Lupus Nephritis/*prevention & control , Mycophenolic Acid/*analogs & derivatives, Albuminuria/prevention & control ; Animals ; Antibodies, Monoclonal/metabolism ; Antigen-Antibody Complex/metabolism ; Autoantibodies/biosynthesis ; Cattle ; Disease Models, Animal ; Hypersensitivity, Delayed ; In Vitro Techniques ; Lupus Nephritis/immunology ; Lupus Nephritis/pathology ; Lymphocyte Activation/drug effects ; Mice ; Mice, Inbred BALB C ; Mice, Inbred MRL lpr ; Mycophenolic Acid/pharmacology ; Serum Albumin, Bovine/immunology ; Spleen/drug effects ; Spleen/immunology |
| مستخلص: | Mycophenolate mofetil (MMF) is the morpholinoethyl ester of mycophenolic acid, which is its active metabolite. MMF is effective in prolonging survival of allografts and xenografts. However, little is known about the effects and the main mechanism of action of MMF in autoimmune diseases. In this study, the effect of MMF on the spontaneous disease progression in the MRL/lpr mouse model of lupus was examined. Eight-week-old MRL/lpr mice (n=18) were orally treated with MMF dissolved in a vehicle (90 mg/kg) once a day. Control animals received vehicle alone (n=17). The incidence of albuminuria (>300 microg/18 h) was significantly reduced by MMF treatment compared with vehicle-treated controls (cumulative incidence of albuminuria at 23 wk in MMF-treated mice; 22% versus 88% in controls; P=0.0001). The glomerulonephritis was histologically less severe in MMF-treated mice than in control mice (P=0.005). Furthermore, in immunofluorescence studies the amount of immunoglobulin and C3 deposits in the glomerular capillary wall was significantly less in MMF-treated mice (P < or = 0.002). Surprisingly, in vivo no clear-cut immune-modulating effects were observed because there were no differences between MMF-treated and control animals with regard to autoantibody formation. Also, spleen enlargement and numbers of CD3+, CD4+, and CD8+ T cells in spleen, lymph nodes, and peripheral blood were not different between both groups. Furthermore, no immunosuppressive properties of 90 mg/kg MMF were found in BALB/c mice on delayed-type hypersensitivity and primary antibody response to methylated bovine serum albumin. Interestingly, renal perfusion experiments revealed that binding of nucleosome/antinucleosome complexes to the glomerular basement membrane is decreased in MMF-treated mice compared with control mice. It is concluded that MMF suppresses the development of lupus glomerulonephritis and albuminuria in MRL/ lpr mice. The observed reduction of glomerular immunoglobulin deposits in MMF-treated mice and the renal perfusion studies indicate that MMF treatment leads to a decreased binding of immune complexes in the glomerular capillary wall in lupus nephritis. |
| المشرفين على المادة: | 0 (Antibodies, Monoclonal) 0 (Antigen-Antibody Complex) 0 (Autoantibodies) 0 (Immunosuppressive Agents) 27432CM55Q (Serum Albumin, Bovine) HU9DX48N0T (Mycophenolic Acid) |
| تواريخ الأحداث: | Date Created: 19980811 Date Completed: 19981104 Latest Revision: 20210518 |
| رمز التحديث: | 20231215 |
| DOI: | 10.1681/ASN.V981407 |
| PMID: | 9697662 |
| قاعدة البيانات: | MEDLINE |
| تدمد: | 1046-6673 |
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| DOI: | 10.1681/ASN.V981407 |