机构：[1]Department of Pharmacology, Chongqing Medical University, Chongqing 400016, China[2]The Key Laboratory of Biochemistry and Molecular Pharmacology, Chongqing 400016, China[3]Department of Neurosurgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China重庆医科大学附属第一医院[4]Center for Clinical Molecular Medicine, Children's Hospital of Chongqing Medical University, Chongqing 400014, China[5]The Pediatrics Research Institute, Ministry of Education Key Laboratory of Child Development and Disorders[6]Department of Laboratory, Children’s Hospital of Chongqing Medical University, Chongqing 400014, China[7]Chongqing Engineering Research Center of Stem Cell Therapy, Chongqing 400014, China[8]Department of Pharmacy, Chongqing Hospital of Traditional Chinese Medicine, Chongqing 400011, China[9]Department of Pharmacy, People’s Hospital of Rongchang District, Chongqing 402460, China[10]State Key Lab of Ophthalmology, Guangdong Provincial Key Lab of Ophthalmology and Visual Science, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou 510000, China
Hydroxychloroquine (HCQ) and human umbilical cord-derived mesenchymal stem cells (UC-MSCs) were used to treat systemic lupus erythematosus (SLE), respectively. However, the effect of HCQ on UC-MSCs in lupus nephritis (LN) has not been investigated. In this study, HCQ and UC-MSCs were used in MRL/lpr mice. Surprisingly, although the treatment of both HCQ and UC-MSCs could ameliorate renal damage separately, the presence of HCQ decreased unexpectedly the therapeutic effects of UC-MSCs through interfering expression of IFN-γ. However, HCQ-pretreated UC-MSCs showed significant improvements of renal morphology and function more rapidly than that of UC-MSCs and HCQ alone. To test the role of HCQ in UC-MSCs, MRL/lpr mice and SLE patients' peripheral blood were used in vivo and in vitro. Results showed that after administration of UC-MSCs pretreated by HCQ, CXCR3 expression in renal tissues, serum IL-2, and IgM levels decreased significantly, and serum IL-10 level increased significantly. HCQ pretreatment caused a significant decrease of TNF-α and MCP-1 secretion and an increase of IL-1β and CXCL10 release from UC-MSCs. Our results indicate that HCQ plays a double-edged role in UC-MSCs. It is necessary for clinical treatment to pre-evaluated concomitant application of UC-MSCs with HCQ. More importantly, the alterative expression of IFN-γ, the improvement of migration ability of UC-MSCs, the regulation of Th1/Th2 balance, and the changes of antibodies secretion in B cell might be involved in its mechanisms.
基金：
Natural Scientific Foundation of China (81373444, 81570372) and
the Ministry of Science and Technology (2016YFA0101300).
语种：
外文
被引次数：
WOS：
PubmedID：
中科院(CAS)分区：
出版当年[2017]版：
大类|2 区医学
小类|2 区医学：研究与实验2 区药学
最新[2025]版：
大类|2 区医学
小类|2 区药学3 区医学：研究与实验
JCR分区：
出版当年[2016]版：
Q1MEDICINE, RESEARCH & EXPERIMENTALQ1PHARMACOLOGY & PHARMACY
最新[2023]版：
Q1PHARMACOLOGY & PHARMACYQ2MEDICINE, RESEARCH & EXPERIMENTAL
第一作者机构：[1]Department of Pharmacology, Chongqing Medical University, Chongqing 400016, China[2]The Key Laboratory of Biochemistry and Molecular Pharmacology, Chongqing 400016, China
共同第一作者：
通讯作者：
通讯机构：[1]Department of Pharmacology, Chongqing Medical University, Chongqing 400016, China[2]The Key Laboratory of Biochemistry and Molecular Pharmacology, Chongqing 400016, China
推荐引用方式(GB/T 7714)：
Mai Shaoshan,Zou Lin,Tian Xiaoyan,et al.Double-Edged Effect of Hydroxychloroquine on Human Umbilical Cord-Derived Mesenchymal Stem Cells Treating Lupus Nephritis in MRL/lpr Mice.[J].MOLECULAR PHARMACEUTICS.2018,15(5):1800-1813.doi:10.1021/acs.molpharmaceut.7b01146.
APA：
Mai Shaoshan,Zou Lin,Tian Xiaoyan,Liao Xiao,Luan Yizhao...&Yang Junqing.(2018).Double-Edged Effect of Hydroxychloroquine on Human Umbilical Cord-Derived Mesenchymal Stem Cells Treating Lupus Nephritis in MRL/lpr Mice..MOLECULAR PHARMACEUTICS,15,(5)
MLA：
Mai Shaoshan,et al."Double-Edged Effect of Hydroxychloroquine on Human Umbilical Cord-Derived Mesenchymal Stem Cells Treating Lupus Nephritis in MRL/lpr Mice.".MOLECULAR PHARMACEUTICS 15..5(2018):1800-1813
