Choi Bunsoon, Kim Hyoun-Ah, Suh Chang-Hee, Byun Hae Ok, Jung Ju-Yang, Sohn Seonghyang
Department of Microbiology, Ajou University School of Medicine, Suwon 443-380, Korea.
Department of Rheumatology, Ajou University School of Medicine, Suwon 443-380, Korea.
Int J Mol Sci. 2015 Apr 2;16(4):7413-27. doi: 10.3390/ijms16047413.
The purpose of this study was to clarify the correlation between microRNA-21 (miR-21) expression and inflammation in a herpes simplex virus (HSV)-induced Behçet's Disease (BD) mouse model. miR-21 was compared between BD patients and healthy controls in peripheral blood mononuclear cells (PBMC). For miR-21 inhibition, miR-21 antagomir was applied to BD mice. The change of symptoms was monitored. The levels of cytokines and related molecules were determined by ELISA and real time qPCR. Treatment with colchicine or pentoxifylline down-regulated the level of miR-21 with improved symptoms in mice. miR-21 inhibition was accompanied by down-regulated serum levels of IL-17 and IL-6. The expression levels of PDCD4, RhoB, PD-1, IL-12p35, and toll-like receptor-4 were also regulated by miR-21 inhibition. miR-21 was correlated with HSV-induced BD-like inflammation in mice and BD patients. The expression of miR-21 was regulated by antagomir in mice.
本研究的目的是阐明单纯疱疹病毒(HSV)诱导的白塞病(BD)小鼠模型中微小RNA-21(miR-21)表达与炎症之间的相关性。比较了BD患者和健康对照外周血单个核细胞(PBMC)中miR-21的表达情况。为抑制miR-21,将miR-21拮抗剂应用于BD小鼠。监测症状变化。通过酶联免疫吸附测定(ELISA)和实时定量聚合酶链反应(qPCR)测定细胞因子和相关分子水平。用秋水仙碱或己酮可可碱治疗可下调小鼠miR-21水平,并改善症状。抑制miR-21伴随着血清白细胞介素-17(IL-17)和白细胞介素-6(IL-6)水平的下调。miR-21抑制还调节了程序性细胞死亡蛋白4(PDCD4)、RhoB、程序性死亡受体1(PD-1)、白细胞介素-12 p35和Toll样受体4(TLR-4)的表达水平。miR-21与小鼠和BD患者中HSV诱导的BD样炎症相关。在小鼠中,miR-21的表达受拮抗剂调节。