Mesenchymal stem cells derived from human bone marrow ameliorate monosodium urate crystal-induced inflammation.

Abstract

Mesenchymal stem cells (MSCs) have anti-inflammatory properties and have been implicated in several inflammatory diseases. Acute gout is initiated by IL-1β produced by monosodium urate crystal (MSU)-stimulated macrophages via activation of NLRP3 inflammasomes. We sought to investigate whether MSCs derived from human bone marrow (hBM-MSCs) suppress MSU-induced inflammation. hBM-MSCs were stimulated with proinflammatory cytokine cocktails or co-cultured with MSU-treated macrophages. Gene and protein expressions of cytokines and NLRP3 inflammasome-related molecules were measured with reverse transcription-polymerase chain reactions, western blot analysis, and cytokine arrays. In vivo therapeutic effects were evaluated in a murine acute gout model. Macrophages stimulated with MSUs produced less cleaved caspase-1(mature caspase-1) and cleaved IL-1β (mature IL-1β) in the presence of hBM-MSCs. Furthermore, macrophages co-cultured with hBM-MSCs produced less TNF-α and IL-6, suggesting that the M1-like phenotype of the macrophages was suppressed. hBM-MSCs produced higher anti-inflammatory cytokine such as IL-1 receptor antagonist in the co-culture system. They also produced high levels of IL-6 in the inflammatory milieu, and the suppression of cleaved IL-1β production by macrophages was abrogated when hBM-MSCs were treated with IL-6 siRNA. Intravenous pre-treatment with hBM-MSCs suppressed MSU-induced acute inflammation in a murine acute gout model. In conclusion, hBM-MSCs suppress MSU-induced inflammation by suppressing the M1-like phenotype of macrophages in a partially IL-6 dependent pathway. Here, we suggest a potential therapeutic use of hBM-MSCs for treatment of acute gout.