Resveratrol (RES) and its antagonist, sirtinol suppress human cytomegalovirus (hCMV) replication and hCMV induced transcription of proinflammatory cytokines and chemokines in THP-1 derived macrophages

Abstract

Abstract Background Mounting evidence suggests significant contribution of chronic hCMV infection to T-cell immunosenenscence and chronic inflammation in old adults. THP-1, a human monocytic cell line and its derived macrophages serve as a useful cell culture model to study hCMV infection and its biology. Novel anti-CMV agents are needed as current anti-CMV treatment is limited in efficacy with significant side effects. We and others observed that Resveratrol (RES) and sirtinol, suppressed CMV replication in human fibroblasts. Here we report their inhibition on hCMV replication and hCMV induced expression of IL-6, IP-10, MCP-1 and TNF-a in THP-1 derived macrophages. Methods THP-1 cells were differentiated into macrophages after incubation with PMA (50 ng/ml) in RPMI 1640 with 10%FBS for 24 hrs. RES or sirtinol was added 2 h followed by hCMV (Towne strain) inoculation at multiplicity of infection of MOI 2 for 24 hrs. Cells were then cultured in hCMV-free medium for indicated times. qPCR and RT-PCR were performed to evaluate hCMV replication and transcription of IL-6, IP-10, MCP-1 and TNF-a, respectively. Results Both RES and sirtinol suppressed hCMV replication. They also suppressed hCMV induced transcription of proinflammatory mediators except for TNF-a. Conclusions and discussion These findings indicate potent inhibition of hCMV infection and hCMV induced transcription of proinflammatory mediators by RES and sirtinol in THP-1 derived macrophages. While being non-permissive, monocytes are important reservoir for chronic or latent CMV infection. Further investigation into the role and mechanisms of RES, sirtinol and other agents in control of chronic CMV infection and its adverse impact is indicated.