NF-κB Inhibitor Pyrrolidinedithiocarbamate Can Increase the Infection and Activation of Cytomegalovirus in Mesenchymal Stem Cells.

Abstract

Objective Because of the central role of the transcription factor nuclear factor-κB (NF-κB) in cell survival and proliferation in many kinds of cancer cells, NF-κB inhibitor may have a potential role in the therapy of cancer. Human cytomegalovirus (CMV) infection is one of the most common complications following stem cells transplantation. Some data report that CMV infection has a very close relation with NF-κB activation. But it is unknown what effect of NF-κB inhibitor pyrrolidinedithiocarbamate (PTDC) on the infection and activation of cytomegalovirus in mesenchymal stem cells(MSCs).Methods MSCs were infected by 1 TCID50 of CMV combined with/without 1μmol/L of PTDC. After 48h of culture with DMEM supplemented with 10% (v/v) fetal calf serum, MSCs shapes were observed. RT-PCR assay was used to detect the mRNA expression of CMV immediate early (IE) gene and GAPDH gene. Flow Cytometry was used to detect the CMV PP65 antigen positive cells.Results Shape of some MSCs changed after the infection of 1 TCID50 of CMV. But in MSCs infected by 1 TCID50 of CMV combined with 1μmol/L of PTDC, Cell shape changed more dominantly, almost all cells changed from thin shuttle shape to round and thick ball shape. While in the cells treated only with PDTC, shape of the cells did not changed. RT-PCR assay showed that there was a very bright band of CMV IE mRNA in MSCs infected by 1 TCID50 of CMV combined with 1μmol/L of PTDC compared with the cells infected only with 1 TCID50 of CMV. More CMV pp65 antigen positive cells were found in MSCs infected by 1 TCID50 of CMV combined with 1μmol/L of PTDC with Flow Cytometry.Conclusion NF-κB activation may affect CMV infection of cells. NF-κB inhibitor PTDC can increase the infection and activation of CMV in MSCs and we should pay more attention to CMV infection when we use NF-κB inhibitor in clinical work..