SM934 treated lupus-prone NZB × NZW F1 mice by enhancing macrophage interleukin-10 production and suppressing pathogenic T cell development.

<h4>Background</h4>Artemisinin and its derivatives were reported to possess strong regulatory effects on inflammation and autoimmune diseases. This study was designed to examine the therapeutic effects and underlying mechanisms of SM934, a water-soluble artemisinin analogue, on lupus-pro...

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Autores principales:	Li-Fei Hou, Shi-Jun He, Xin Li, Chun-Ping Wan, Yang Yang, Xiao-Hui Zhang, Pei-Lan He, Yu Zhou, Feng-Hua Zhu, Yi-Fu Yang, Ying Li, Wei Tang, Jian-Ping Zuo
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2012
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/c5456729a7064a86821d9c88ed18c41e
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spelling	oai:doaj.org-article:c5456729a7064a86821d9c88ed18c41e2021-11-18T07:26:32ZSM934 treated lupus-prone NZB × NZW F1 mice by enhancing macrophage interleukin-10 production and suppressing pathogenic T cell development.1932-620310.1371/journal.pone.0032424https://doaj.org/article/c5456729a7064a86821d9c88ed18c41e2012-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22389703/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203<h4>Background</h4>Artemisinin and its derivatives were reported to possess strong regulatory effects on inflammation and autoimmune diseases. This study was designed to examine the therapeutic effects and underlying mechanisms of SM934, a water-soluble artemisinin analogue, on lupus-prone female NZB × NZW F(1) mice.<h4>Methodology/principal findings</h4>NZB/W F(1) mice were treated orally with SM934 for 3 or 6 months respectively to investigate the effect on clinical manifestations and immunological correlates. To further explore the mechanisms of SM934, ovalbumin (OVA)-immunized or interferon (IFN)-γ-elicited C57BL/6 mice were used. In vivo, treatment with SM934 for 3 or 6 months significantly delayed the progression of glomerulonephritis and increased the survival rate of NZB/W F(1) mice. Clinical improvement was accompanied with decreased Th1-related anti-double-strand DNA (dsDNA) IgG2a and IgG3 Abs, serum interleukin (IL)-17, and increased Th2-related anti-dsDNA IgG1 Ab, serum IL-10 and IL-4. SM934 treatment also suppressed the accumulation of effector/memory T cells, induced the apoptosis of CD4(+) T cells, while enhancing the development of regulatory T cells in NZB/W F(1) mice. In addition, SM934 treatment promoted the IL-10 production of macrophages from NZB/W F(1) mice, OVA-immunized C57BL/6 mice and IFN-γ-elicited C57BL/6 mice. In vitro, SM934 enhanced IL-10 production from primary macrophages stimulated with IFN-γ.<h4>Conclusions/significance</h4>The results of this study demonstrated that artemisinin analogue SM934 had therapeutic effects on lupus-prone female NZB/W F(1) mice by inhibiting the pathogenic helper T cell development and enhancing anti-inflammatory cytokine IL-10 production.Li-Fei HouShi-Jun HeXin LiChun-Ping WanYang YangXiao-Hui ZhangPei-Lan HeYu ZhouFeng-Hua ZhuYi-Fu YangYing LiWei TangJian-Ping ZuoPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 7, Iss 2, p e32424 (2012)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Li-Fei Hou Shi-Jun He Xin Li Chun-Ping Wan Yang Yang Xiao-Hui Zhang Pei-Lan He Yu Zhou Feng-Hua Zhu Yi-Fu Yang Ying Li Wei Tang Jian-Ping Zuo SM934 treated lupus-prone NZB × NZW F1 mice by enhancing macrophage interleukin-10 production and suppressing pathogenic T cell development.
description	<h4>Background</h4>Artemisinin and its derivatives were reported to possess strong regulatory effects on inflammation and autoimmune diseases. This study was designed to examine the therapeutic effects and underlying mechanisms of SM934, a water-soluble artemisinin analogue, on lupus-prone female NZB × NZW F(1) mice.<h4>Methodology/principal findings</h4>NZB/W F(1) mice were treated orally with SM934 for 3 or 6 months respectively to investigate the effect on clinical manifestations and immunological correlates. To further explore the mechanisms of SM934, ovalbumin (OVA)-immunized or interferon (IFN)-γ-elicited C57BL/6 mice were used. In vivo, treatment with SM934 for 3 or 6 months significantly delayed the progression of glomerulonephritis and increased the survival rate of NZB/W F(1) mice. Clinical improvement was accompanied with decreased Th1-related anti-double-strand DNA (dsDNA) IgG2a and IgG3 Abs, serum interleukin (IL)-17, and increased Th2-related anti-dsDNA IgG1 Ab, serum IL-10 and IL-4. SM934 treatment also suppressed the accumulation of effector/memory T cells, induced the apoptosis of CD4(+) T cells, while enhancing the development of regulatory T cells in NZB/W F(1) mice. In addition, SM934 treatment promoted the IL-10 production of macrophages from NZB/W F(1) mice, OVA-immunized C57BL/6 mice and IFN-γ-elicited C57BL/6 mice. In vitro, SM934 enhanced IL-10 production from primary macrophages stimulated with IFN-γ.<h4>Conclusions/significance</h4>The results of this study demonstrated that artemisinin analogue SM934 had therapeutic effects on lupus-prone female NZB/W F(1) mice by inhibiting the pathogenic helper T cell development and enhancing anti-inflammatory cytokine IL-10 production.
format	article
author	Li-Fei Hou Shi-Jun He Xin Li Chun-Ping Wan Yang Yang Xiao-Hui Zhang Pei-Lan He Yu Zhou Feng-Hua Zhu Yi-Fu Yang Ying Li Wei Tang Jian-Ping Zuo
author_facet	Li-Fei Hou Shi-Jun He Xin Li Chun-Ping Wan Yang Yang Xiao-Hui Zhang Pei-Lan He Yu Zhou Feng-Hua Zhu Yi-Fu Yang Ying Li Wei Tang Jian-Ping Zuo
author_sort	Li-Fei Hou
title	SM934 treated lupus-prone NZB × NZW F1 mice by enhancing macrophage interleukin-10 production and suppressing pathogenic T cell development.
title_short	SM934 treated lupus-prone NZB × NZW F1 mice by enhancing macrophage interleukin-10 production and suppressing pathogenic T cell development.
title_full	SM934 treated lupus-prone NZB × NZW F1 mice by enhancing macrophage interleukin-10 production and suppressing pathogenic T cell development.
title_fullStr	SM934 treated lupus-prone NZB × NZW F1 mice by enhancing macrophage interleukin-10 production and suppressing pathogenic T cell development.
title_full_unstemmed	SM934 treated lupus-prone NZB × NZW F1 mice by enhancing macrophage interleukin-10 production and suppressing pathogenic T cell development.
title_sort	sm934 treated lupus-prone nzb × nzw f1 mice by enhancing macrophage interleukin-10 production and suppressing pathogenic t cell development.
publisher	Public Library of Science (PLoS)
publishDate	2012
url	https://doaj.org/article/c5456729a7064a86821d9c88ed18c41e
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SM934 treated lupus-prone NZB × NZW F1 mice by enhancing macrophage interleukin-10 production and suppressing pathogenic T cell development.

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