CTLA4 silencing with siRNA promotes deviation of Th1/Th2 in chronic hepatitis B patients.
To determine whether RNA interference (RNAi) could block cytotoxic T-lymphocyte antigen 4 (CTLA4) in human lymphocytes in vitro and promote IFN-gamma and IL-2 secretions, three small interfering RNAs (siRNAs) were selected based on target specificity sequences of human CTLA4 and transfected into human lymphocytes of chronic HBV patients. As a result, the expression of human CTLA4 mRNA was efficiently suppressed by all the three siRNAs. Compared with negative control (siRNA-co), siRNA-1 inhibited the expression of CTLA4 most efficiently and was used in the further study. The expressions of IFN-gamma and IL-2 were upregulated and the level of IL-4 was almost unchanged in lymphocytes transfected with siRNA-1 compared with the blank control. These results indicated that siRNA-1 led to IFN-gamma and IL-2 secretions, which is a main response of Th1/Th2. In a conclusion, RNAi significantly suppressed the expression of human CTLA4 mRNA in human lymphocytes in vitro, and could induce Th1/Th2 response. It could be a new therapeutic strategy for chronic HBV infection.
Yu
Yongsheng
Y
Department of Infectious Diseases, Sixth People's Hospital, Shanghai Jiaotong University, Shanghai 200233, China. yuyongsheng@medmail.com.cn
Wu
Hao
H
Tang
Zhenghao
Z
Zang
Guoqing
G
D000328:Adult; D000368:Aged; D015703:Antigens, CD / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D060908:CTLA-4 Antigen; D002454:Cell Differentiation; D016207:Cytokines / Q000378:metabolism; D004279:DNA, Viral / Q000097:blood* / Q000276:immunology; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D020868:Gene Silencing; D006515:Hepatitis B virus / Q000276:immunology; D019694:Hepatitis B, Chronic / Q000097:blood / Q000235:genetics / Q000276:immunology*; D006801:Humans; D008213:Lymphocyte Activation; D008297:Male; D008875:Middle Aged; D034741:RNA, Small Interfering / Q000235:genetics; D018417:Th1 Cells / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D018418:Th2 Cells / Q000276:immunology / Q000378:metabolism* / Q000473:pathology
D015703:Antigens, CD; D060908:CTLA-4 Antigen; C556706:CTLA4 protein, human; D016207:Cytokines; D004279:DNA, Viral; D034741:RNA, Small Interfering