Published online May 7, 2016. doi: 10.3748/wjg.v22.i17.4354
Peer-review started: December 31, 2015
First decision: January 28, 2016
Revised: February 22, 2016
Accepted: March 14, 2016
Article in press: March 14, 2016
Published online: May 7, 2016
AIM: To investigate the role of miR-125b 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 miR-125b expression in these cells were analyzed. The requirement of Toll-like receptor 2 (TLR2) or MyD88 gene for HCV core protein-induced immune responses was determined by the transfection of THP-1 cells with gene knockdown vectors expressing either TLR2 siRNA or MyD88 siRNA. The effect of miR-125b overexpression on TLR2/MyD88 signaling was examined by transfecting THP-1 cells with miR-125b mimic RNA oligos.
RESULTS: In response to HCV core protein stimulation, cytokine production was up-regulated and miR-125b 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 MyD88 gene. Forced miR-125b 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 MyD88-mediated signaling, including phosphorylation of NF-κBp65, ERK, and P38.
CONCLUSION: The inverse correlation between miR-125b and cytokine expression after HCV core challenge suggests that miR-125b may negatively regulate HCV-induced immune responses by targeting TLR2/MyD88 signaling in monocytes.
Core tip: Increasingly many studies have shown that microRNAs are critical regulators of the innate immune response. Many anti-pathogen pathways, including the pattern recognition Toll-like receptor (TLR)-mediated signaling pathway, are known to be regulated by a network of microRNAs. Here we investigated the possible role of miR-125b in regulating the monocyte immune responses induced by HCV core protein through TLR2/MyD88 signaling. Our findings indicated that miR-125b may function as a negative regulator of HCV-induced cellular events, which may provide insight into the role of miR-125b in the innate immune responses of monocytes to HCV.