Prevention of immune nephritis by the small molecular weight immunomodulator iguratimod in MRL/lpr mice.

<h4>Objective</h4>This study was performed to investigate the therapeutic effects of iguratimod in a lupus mouse model.<h4>Methods</h4>Female MRL/lpr mice were treated with iguratimod, vehicle solution or cyclophosphamide. Proteinuria was monitored and kidney injury was blind...

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Autores principales:	Qingran Yan, Fang Du, Xinfang Huang, Qiong Fu, Sheng Chen, Dai Dai, Chunde Bao
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2014
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/ec484e5589ca43fb8bbf01df96b8bc29
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spelling	oai:doaj.org-article:ec484e5589ca43fb8bbf01df96b8bc292021-11-25T05:58:24ZPrevention of immune nephritis by the small molecular weight immunomodulator iguratimod in MRL/lpr mice.1932-620310.1371/journal.pone.0108273https://doaj.org/article/ec484e5589ca43fb8bbf01df96b8bc292014-01-01T00:00:00Zhttps://doi.org/10.1371/journal.pone.0108273https://doaj.org/toc/1932-6203<h4>Objective</h4>This study was performed to investigate the therapeutic effects of iguratimod in a lupus mouse model.<h4>Methods</h4>Female MRL/lpr mice were treated with iguratimod, vehicle solution or cyclophosphamide. Proteinuria was monitored and kidney injury was blindly scored by a renal pathologist. Serum anti-double-stranded DNA antibodies were monitored by radioimmunoassay. Kidney IgG and CD20 were stained by immunohistochemistry. Splenic lymphocyte phenotypes were analyzed by flow cytometry. BAFF, IL-17A, IL-6, and IL-21 levels in serum and splenic lymphocytes were detected by ELISA or quantitative PCR.<h4>Results</h4>Compared with the vehicle-treated controls, MRL/lpr mice treated with iguratimod showed less protenuria, less acute pathological lesions and no chronic changes in the kidneys. There were significant differences in glomerular injury and vasculitis scores, as well as in the semi-quantitative analysis of immune complex deposition between the two groups. Disease activity markers in sera (anti-dsDNA antibodies and immunoglobulin levels) were reduced and hypocomplementemia was attenuated. Lymphocyte expression of BAFF, IL-6, IL-17A and IL-21 was decreased. The abnormal splenic B220+ T cell and plasma cell populations in MRL/lpr mice were reduced by iguratimod treatment, with recovery of the total B cell population and inhibition of B cell infiltration of the kidney tissue. The dosage of iguratimod used in this study showed no significant cytotoxic effects in vivo and no overt side-effects were observed.<h4>Conclusion</h4>Iguratimod ameliorates immune nephritis in MRL/lpr mice via a non-antiproliferative mechanism. Our data suggest a potential therapeutic role of iguratimod in lupus.Qingran YanFang DuXinfang HuangQiong FuSheng ChenDai DaiChunde BaoPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 9, Iss 10, p e108273 (2014)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Qingran Yan Fang Du Xinfang Huang Qiong Fu Sheng Chen Dai Dai Chunde Bao Prevention of immune nephritis by the small molecular weight immunomodulator iguratimod in MRL/lpr mice.
description	<h4>Objective</h4>This study was performed to investigate the therapeutic effects of iguratimod in a lupus mouse model.<h4>Methods</h4>Female MRL/lpr mice were treated with iguratimod, vehicle solution or cyclophosphamide. Proteinuria was monitored and kidney injury was blindly scored by a renal pathologist. Serum anti-double-stranded DNA antibodies were monitored by radioimmunoassay. Kidney IgG and CD20 were stained by immunohistochemistry. Splenic lymphocyte phenotypes were analyzed by flow cytometry. BAFF, IL-17A, IL-6, and IL-21 levels in serum and splenic lymphocytes were detected by ELISA or quantitative PCR.<h4>Results</h4>Compared with the vehicle-treated controls, MRL/lpr mice treated with iguratimod showed less protenuria, less acute pathological lesions and no chronic changes in the kidneys. There were significant differences in glomerular injury and vasculitis scores, as well as in the semi-quantitative analysis of immune complex deposition between the two groups. Disease activity markers in sera (anti-dsDNA antibodies and immunoglobulin levels) were reduced and hypocomplementemia was attenuated. Lymphocyte expression of BAFF, IL-6, IL-17A and IL-21 was decreased. The abnormal splenic B220+ T cell and plasma cell populations in MRL/lpr mice were reduced by iguratimod treatment, with recovery of the total B cell population and inhibition of B cell infiltration of the kidney tissue. The dosage of iguratimod used in this study showed no significant cytotoxic effects in vivo and no overt side-effects were observed.<h4>Conclusion</h4>Iguratimod ameliorates immune nephritis in MRL/lpr mice via a non-antiproliferative mechanism. Our data suggest a potential therapeutic role of iguratimod in lupus.
format	article
author	Qingran Yan Fang Du Xinfang Huang Qiong Fu Sheng Chen Dai Dai Chunde Bao
author_facet	Qingran Yan Fang Du Xinfang Huang Qiong Fu Sheng Chen Dai Dai Chunde Bao
author_sort	Qingran Yan
title	Prevention of immune nephritis by the small molecular weight immunomodulator iguratimod in MRL/lpr mice.
title_short	Prevention of immune nephritis by the small molecular weight immunomodulator iguratimod in MRL/lpr mice.
title_full	Prevention of immune nephritis by the small molecular weight immunomodulator iguratimod in MRL/lpr mice.
title_fullStr	Prevention of immune nephritis by the small molecular weight immunomodulator iguratimod in MRL/lpr mice.
title_full_unstemmed	Prevention of immune nephritis by the small molecular weight immunomodulator iguratimod in MRL/lpr mice.
title_sort	prevention of immune nephritis by the small molecular weight immunomodulator iguratimod in mrl/lpr mice.
publisher	Public Library of Science (PLoS)
publishDate	2014
url	https://doaj.org/article/ec484e5589ca43fb8bbf01df96b8bc29
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Prevention of immune nephritis by the small molecular weight immunomodulator iguratimod in MRL/lpr mice.

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