The transcriptional and post-translational regulation of the IL-6 gene is complex and involves a lot of signaling proteins and transcriptional factors. It has been recently shown that the ZC3H11A (ZC3) protein supports growth of multiple nuclear replicating human viruses like influenza virus, adenovirus (HAdV), herpes simplex virus and HIV. In addition ZC3 was shown to be up regulated as a result of applying heat stress on the cells. In another work where there was an attempt to pull down the proteins associated with Il6 mRNA, ZC3 was one the potential proteins associated with IL6 mRNA. Here we will test the effect of ZC3 in the regulation of proinflammatory cytokines with much focus on IL6.
To test that we will study the secretion of IL6 in wild type Hela cells compared to Hela ZC3 KO cells upon stimulation with different stimulants IL1b, LPS, poly I:C, and TNF. We also will test the other proinflammatory cytokines in different cell model THP1 cells (Human leukemic monocytes) using siRNA ZC3 and lentivirus expressing sh RNA for ZC3. We are also interested to explore the effect of ZC3 on the transcription factors of IL6.