Activation of DC-SIGN promoter and common signaling pathways between HIV-1 5'LTR and DC-SIGN

Abstract

Objective: To explore whether expression of dendritic cell-specific intercellular adhesion molecule-3-grabbing non-integrin (DC-SIGN) and reactivation of human immunodeficiency virus type 1 (HIV-1) provirus in dendritic cells (DCs) occur through similar or common signaling pathways. Methods: Phorbol 12-myristate 13-acetate (PMA)-differentiated THP-1 cells were used as the in vitro model of DCs. The activation of the DC-SIGN promoter and HIV-1 5' long-term repeat (LTR) sequence induced by interleukin 4 (IL-4) in differentiated THP-1 cells was studied using luciferase reporter plasmids. The regulatory signaling pathways were identified using specific inhibitors, and the activity of the DC-SIGN promoter and HIV-1 5'LTR was detected. Results: HI V-1 5'LTR was activated by I L-4-induced signaling pathways but much weaker than DC-SIGN promoter. IL-4-induced activation of HIV-1 5'LTR was mainly through the nuclear factor kappalight-chain-enhancer of activated B cells (NF-κB) pathway, which was also involved in activation of the DC-SIGN promoter. The extracellular signal-regulated kinase (ERK) pathway, which was the main pathway for DC-SIGN promoter activation, also played an important role in H I V-1 5'LTR activation. Conclusion: Our study suggests that the activation of the DC-SIGN promoter and HIV-1 5'LTR may share NF-κB and ERK-signaling pathways.