miR-155 regulates pro- and anti-inflammatory cytokine expression in human monocytes during chronic hepatitis C virus infection.

Background: Hepatitis C virus (HCV) dysregulates innate and adaptive immune responses while monocytes (M) play a crucial role in linking innate and adaptive immunity to control viral infection. A transcription factor T-bet is upregulated to dampen M functions via the c-Jun N-terminal kinase (JNK) pathway, followed by enhanced Tim-3 expression in chronic HCV infection. However, the molecular mechanisms that control the expression in M are yet unknown. miR-155 has been implicated as a key regulator controlling diverse biological processes through posttranscriptional repression, but the influences of miR-155 on these regulators and effectors still need to be studied.

Methods: Forty HCV-infected patients and 40 healthy subjects (HS) were recruited, THP-1 cells (human acute monocyte leukemia cell line) were cultured with HCV-infected Huh 7.5 cells. The expression levels of miR-155 and // were measured by real-time RT-PCR. IL-10/IL-12 was detected by flow cytometry. THP-1 cells were transfected with mimics-155 and negative control, SOCS1, p-STAT1, p65, p-smad, p-p38, and p-JNK were measured by Western blot. TNF-α levels were measured by ELISA. Student's -test was used in statistics.

Results: The study showed that miR-155 was upregulated in CD14 M in HCV-infected patients compared to healthy subjects (P<0.05). Moreover, the upregulation of miR-155 in CD14 M from HCV-infected patients induced TNF-α production and gene expression, which, in turn, led to T-bet upregulation. Also, miR-155 upregulation in CD14 M of HCV-infected patients increased the IL-12 and decreased the IL-10 production.

Conclusions: The obtained results indicated that miR-155 upregulation in M during HCV infection enhances the activation of TNF-α and JNK pathways, promotes the expression of transcription factor T-bet, and triggers pro- and anti-inflammatory mediators. Together, these data reveal new information regarding the mechanisms of chronic HCV infection.