Mol Pharm. 2018 Apr 18. doi: 10.1021/acs.molpharmaceut.7b01146. [Epub ahead of print]

The double-edged effect of hydroxychloroquine on human umbilical cord-derived mesenchymal stem cells treating lupus nephritis in MRL/lpr mice.

Mai S, Zou L, Tian X, Liao X, Luan Y, Han X, Wei Y, Wu Y, Kuang S, Yang Y, Ma J, Chen Q, Yang J.

Abstract

Hydroxychlorquine(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 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 play 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.