Double-Edged Effect of Hydroxychloroquine on Human Umbilical Cord-Derived Mesenchymal Stem Cells Treating Lupus Nephritis in MRL/lpr Mice

Apr 19, 2018Molecular pharmaceutics

Hydroxychloroquine's mixed effects on umbilical cord stem cells treating kidney inflammation in lupus mice

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Abstract

HCQ significantly alters the therapeutic effects of UC-MSCs in treating lupus nephritis in MRL/lpr mice.

Both HCQ and UC-MSCs can reduce renal damage when used separately.
The combination of HCQ with UC-MSCs unexpectedly diminishes the effectiveness of UC-MSCs by interfering with IFN-γ expression.
HCQ-pretreated UC-MSCs lead to faster improvements in renal morphology and function compared to UC-MSCs or HCQ alone.
After treatment with HCQ-pretreated UC-MSCs, levels of CXCR3 in renal tissues, serum IL-2, and IgM decrease significantly, while serum IL-10 increases.
HCQ pretreatment results in decreased secretion of TNF-α and MCP-1, and increased release of IL-1β and CXCL10 from UC-MSCs.

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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.

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Double-Edged Effect of Hydroxychloroquine on Human Umbilical Cord-Derived Mesenchymal Stem Cells Treating Lupus Nephritis in MRL/lpr Mice

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