AIM: To investigate the role of mi R-125 b in regulating monocyte immune responses induced by hepatitis C virus(HCV) core protein.METHODS: Monocytic THP-1 cells were treated with various concentrations of recombinant HCV core protein, and cytokines and mi R-125 b expression in these cells were analyzed. The requirement of Tolllike receptor 2(TLR2) or My D88 gene for HCV core protein-induced immune responses was determined by the transfection of THP-1 cells with gene knockdown vectors expressing either TLR2 si RNA or My D88 si RNA. The effect of mi R-125 b overexpression on TLR2/My D88 signaling was examined by transfecting THP-1 cells with mi R-125 b mimic RNA oligos.RESULTS: In response to HCV core protein stimulation, cytokine production was up-regulated and mi R-125 b expression was down-regulated in THP-1 cells. The modulatory effect of HCV core protein on cellular events was dose-dependent and required functional TLR2 or My D88 gene. Forced mi R-125 b expression abolished the HCV core protein-induced enhancement of tumor necrosis factor-α, interleukin(IL)-6, and IL-10 expression by 66%, 54%, and 66%, respectively(P < 0.001), by inhibiting My D88-mediated signaling, including phosphorylation of NF-k Bp65, ERK, and P38.CONCLUSION: The inverse correlation between mi R-125 b and cytokine expression after HCV core challenge suggests that mi R-125 b may negatively regulate HCVinduced immune responses by targeting TLR2/My D88 signaling in monocytes. AIM: To investigate the role of mi R-125 b in regulating monocyte immune responses induced by hepatitis C virus (HCV) core protein. METHODS: Monocytic THP-1 cells were treated with various concentrations of recombinant HCV core protein, and cytokines and mi The requirement of Tolllike receptor 2 (TLR2) or My D88 gene for HCV core protein-induced immune responses was determined by the transfection of THP-1 cells with gene knockdown vectors either either TLR2 si RNA or My D88 si RNA. The effect of mi R-125 b overexpression on TLR2 / My D88 signaling was examined by transfecting THP-1 cells with mi R-125 b mimic RNA oligos. RESULTS: In response to HCV core protein stimulation, Cytokine production was up-regulated and mi R-125 b expression was down-regulated in THP-1 cells. The modulatory effect of HCV core protein on cellular events was dose-dependent and required functional TLR2 or My D88 gene. Forced mi R- 125 b expression abolished the HCV core protein-induced enhancement of tumor necrosis factor-α, interleukin (IL) -6, and IL-10 expression by 66%, 54%, and 66% including phosphorylation of NF-k Bp65, ERK, and P38. CONCLUSION: The inverse correlation between mi R-125 b and cytokine expression after HCV core challenge suggests that mi R-125 b may negatively regulate HCV induced immune responses by targeting TLR2 / My D88 signaling in monocytes.