OPPOSING REGULATORY EFFECTS OF THIOREDOXIN AND EOSINOPHIL CYTOTOXICITY-ENHANCING FACTOR ON THE DEVELOPMENT OF HUMAN-IMMUNODEFICIENCY-VIRUS-1

被引:48
作者
NEWMAN, GW
BALCEWICZSABLINSKA, MK
GUARNACCIA, JR
REMOLD, HG
SILBERSTEIN, DS
机构
[1] BRIGHAM & WOMENS HOSP,DEPT RHEUMATOL & IMMUNOL,BOSTON,MA 02115
[2] HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA 02115
[3] HARVARD UNIV,SCH PUBL HLTH,DEPT TROP PUBL HLTH,BOSTON,MA 02115
关键词
D O I
10.1084/jem.180.1.359
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Exogenous recombinant human thioredoxin (rTRX, greater than or equal to 500 nM), a dithiol reductase enzyme, inhibited the expression of human immunodeficiency virus (HIV) 1(BaL) in human macrophages (M phi) by 71% (range, 26-100%), as evaluated by p24 antigen production and the integration of provirus at 14 d after infection. The stoichiometric reducing agent N-acetylcysteine (NAC) also inhibited HIV production, but to a lesser degree, and only at 30,000-fold higher concentrations. Exogenous rTRX is cleaved by M phi to generate the inflammatory cytokine, eosinophil cytotoxicity-enhancing factor (ECEF). In contrast to rTRX, rECEF (concentrations from 50 pM to 2 mu M) enhanced the production of HIV by 67% (range, 33-92%). Thus, whereas TRX is a potent inhibitor of the expression of HIV in human M phi, cleavage of TRX to ECEF creates a mediator with the opposite effect. TRX also inhibited the expression of integrated provirus in the chronically infected OM 10.1 cell line, showing that it can act at a step subsequent to viral infection and integration.
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页码:359 / 363
页数:5
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