The effects of signaling pathways activating DC-SIGN promoter on the activity of HIV-1 5'LTR
10.3760/cma.j.issn.0254-5101.2013.05.002
- VernacularTitle:DC-SIGN启动子活化信号通路对HIV-1 5'LTR活性的影响
- Author:
Lijuan WU
;
Shi BAI
;
Fumin LIU
;
Lixiang WU
;
Xinjuan WANG
;
Changzhong JIN
- Publication Type:Journal Article
- Keywords:
DC-SIGN;
HIV-1 latency;
Signaling pathways;
Dendritic cells;
Reactivation
- From:
Chinese Journal of Microbiology and Immunology
2013;(5):326-329
- CountryChina
- Language:Chinese
-
Abstract:
Objective To explore the effects of signaling pathways inducing activation of DC-SIGN promoter on the activity of HIV-1 5'LTR.Methods The sequences of DC-SIGN promoter and HIV-1 5'LTR were amplified by PCR and then cloned into pGL-3/Basic plasmid to constructluciferase reporter plasmids for DC-SIGN promoter and HIV-1 5'LTR.Differentiated THP-1 cells stimulated by PMA (phorbol myristate acetate) were used as the in vitro model of DCs.The activaties of DC-SIGN promoter and HIV-1 5'LTR induced by IL-4 in differentiated THP-1 cells were studied using luciferase reporter plasmids.The signaling pathways were identified by using specific inhibitors.Results IL-4 induced signaling pathways could increase the activities of HIV-1 5'LTR and DC-SIGN promoter for more than two times in THP-1 cells transfected with luciferase reporter plasmids.However,the activity of HIV-1 5'LTR was weaker than that of DCSIGN promoter.ERK/JAK-STAT/NF-κB signal pathway blockers could inhibit the luciferase activity driven by DC-SIGN promoter,of which ERKI/2 blocker showed the strongest inhibitory effect that almost completely blocked IL-4 induction.NF-κB blocker had a significant inhibitory effect on HIV-1 5'LTR activity at a rate of 52.32%,followed by the ERK blocker at a rate of 43.31%.Conclusion This study suggested that IL-4-induced signaling pathways mediate the activation of DC-SIGN promoter and HIV-1 5'LTR through NFκB and ERK.