TY - JOUR
T1 - Retinoic acid treatment protects MRL/lpr lupus mice from the development of glomerular disease
AU - Pérez De Lema, Guillermo
AU - Lucio-Cazaña, Francisco Javier
AU - Molina, Ana
AU - Luckow, Bruno
AU - Schmid, Holger
AU - De Wit, Cor
AU - Moreno-Manzano, Victoria
AU - Banas, Bernhard
AU - Mampaso, Francisco
AU - Schlöndorff, Detlef
N1 - Funding Information:
G.P.d.L. was supported by a postdoctoral fellowship from the Spanish Ministerio de Educación y Cultura (Grant EX 97 7230290). This work was supported in part by grants from the Deutsche Forschungsgemeinschaft to B.B. and D.S. (BA2137/1–1) and to B.L. (LU612/4–1), from the Spanish Ministerio de Ciencia y Tecnología (SAF2001-1048-C03-02), FIS-Instituto Salud Carlos III (PI02-0346) and Comunidad de Madrid (08.3/0011.1/2001) to F.M., and by a bilateral exchange program between Spain (HA00-003) and Germany (DAAD 314/AI-e-dr/ia). We thank S. Chilla and S. Sauer for excellent technical assistance, and Dr. Peter J. Nelson for helpful discussion.
Copyright:
Copyright 2017 Elsevier B.V., All rights reserved.
PY - 2004/9
Y1 - 2004/9
N2 - Background. Retinoic acid (tRA) is an active metabolite of vitamin A with potent anti-inflammatory properties. We analyzed the effects of tRA on the development of lupus nephritis in MRL/lpr mice. Methods. MRL/lpr mice received chow supplemented with vehicle or tRA (daily 10 mg/kg) from 8 to 14 weeks until their sacrifice. MRL/wt mice served as an additional control. Results. tRA-treated MRL/lpr mice showed reduced lymphoadenopathy and splenomegaly as compared to vehicle-treated controls. Treatment reduced proteinuria to almost basal levels. Plasma IgG and anti-DNA antibodies increased comparably in both vehicle and tRA-treated mice. Vehicle-treated mice showed characteristic renal lesions. In contrast tRA-treated mice showed almost normal glomerular histology with a pronounced reduction in endocapillary cell proliferation. T-cell and macrophage infiltrates were reduced after tRA treatment within glomeruli and interstitium as compared to vehicle-treated animals. In spite of this, immune complex and complement deposition were comparable in both groups. Adoptively transferred T cells from vehicle-treated to tRA-treated MRL/lpr mice did not induce renal lesions or proteinuria. These beneficial effects of tRA treatment were associated with reduced renal expression of chemokines and inflammatory cytokines. Surprisingly, renal transforming growth factor-β (TGF-β) mRNA levels of tRA-treated mice were elevated, possibly indicating that TGF-β acts as an anti-inflammatory signal in this lupus model. Conclusion. tRA treatment reduces lymphoproliferation and glomerulonephritis in MRL/lpr mice. This occurs in spite of unaltered anti-DNA titers and glomerular immune complex deposition, and cannot be overcome by T-cell transfer from nephritic MRL/lpr mice.
AB - Background. Retinoic acid (tRA) is an active metabolite of vitamin A with potent anti-inflammatory properties. We analyzed the effects of tRA on the development of lupus nephritis in MRL/lpr mice. Methods. MRL/lpr mice received chow supplemented with vehicle or tRA (daily 10 mg/kg) from 8 to 14 weeks until their sacrifice. MRL/wt mice served as an additional control. Results. tRA-treated MRL/lpr mice showed reduced lymphoadenopathy and splenomegaly as compared to vehicle-treated controls. Treatment reduced proteinuria to almost basal levels. Plasma IgG and anti-DNA antibodies increased comparably in both vehicle and tRA-treated mice. Vehicle-treated mice showed characteristic renal lesions. In contrast tRA-treated mice showed almost normal glomerular histology with a pronounced reduction in endocapillary cell proliferation. T-cell and macrophage infiltrates were reduced after tRA treatment within glomeruli and interstitium as compared to vehicle-treated animals. In spite of this, immune complex and complement deposition were comparable in both groups. Adoptively transferred T cells from vehicle-treated to tRA-treated MRL/lpr mice did not induce renal lesions or proteinuria. These beneficial effects of tRA treatment were associated with reduced renal expression of chemokines and inflammatory cytokines. Surprisingly, renal transforming growth factor-β (TGF-β) mRNA levels of tRA-treated mice were elevated, possibly indicating that TGF-β acts as an anti-inflammatory signal in this lupus model. Conclusion. tRA treatment reduces lymphoproliferation and glomerulonephritis in MRL/lpr mice. This occurs in spite of unaltered anti-DNA titers and glomerular immune complex deposition, and cannot be overcome by T-cell transfer from nephritic MRL/lpr mice.
UR - http://www.scopus.com/inward/record.url?scp=4344693283&partnerID=8YFLogxK
U2 - 10.1111/j.1523-1755.2004.00850.x
DO - 10.1111/j.1523-1755.2004.00850.x
M3 - Journal articles
AN - SCOPUS:4344693283
SN - 0085-2538
VL - 66
SP - 1018
EP - 1028
JO - Kidney International
JF - Kidney International
IS - 3
ER -