L-2-oxothiazolidine-4-carboxylic acid (procysteine) inhibits expression of the human immunodeficiency virus and expression of the interleukin-2 receptor alpha chain.
These studies were undertaken to examine the in vitro effects of the cysteine pro-drug L-2-oxothiazolidine-4-carboxylic acid (Procysteine) on human immunodeficiency virus expression. Procysteine inhibited HIV expression in human peripheral blood mononuclear cells as detected by measurement of supernatant core antigen. In transient transfection assays, Procysteine inhibited gene expression controlled by the HIV-1 promoter in activated Jurkat cells but not in resting Jurkat cells. Gel-shift assays showed that Procysteine inhibited NF-kappa B DNA binding activity in nuclear extracts. Procysteine did not affect the production of interleukin-2 by peripheral blood mononuclear cells of healthy HIV-seronegative subjects, as measured by bioassay but it decreased the density of cell-surface interleukin-2 receptors detected by flow cytometry after stimulation with phytohemagglutinin (PHA). Thus, Procysteine inhibits HIV expression, HIV promoter activity, and NF-kappa B binding activity in vitro. Procysteine does not affect interleukin-2 production but inhibits interleukin-2 receptor expression in PHA-stimulated peripheral blood mononuclear cells.
Department of Medicine, Case Western Reserve University School of Medicine, Cleveland, OH 44106-4984.
M M
MM
Lederman
D
D
Georges
S
S
Dando
R
R
Schmelzer
L
L
Averill
D
D
Goldberg
D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D015870:Gene Expression / Q000187:drug effects; D016655:HIV Core Protein p24 / Q000032:analysis; D015658:HIV Infections / Q000821:virology*; D015497:HIV-1 / Q000187:drug effects* / Q000235:genetics / Q000254:growth & development; D006801:Humans; D007376:Interleukin-2 / Q000494:pharmacology; D007963:Leukocytes, Mononuclear / Q000821:virology*; D008213:Lymphocyte Activation / Q000187:drug effects; D016328:NF-kappa B / Q000378:metabolism; D010835:Phytohemagglutinins / Q000494:pharmacology; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D011761:Pyrrolidonecarboxylic Acid; D015375:Receptors, Interleukin-2 / Q000096:biosynthesis / Q000187:drug effects*; D013601:T-Lymphocytes / Q000821:virology; D013844:Thiazoles / Q000494:pharmacology*; D053778:Thiazolidines; D014779:Virus Replication / Q000187:drug effects
D016655:HIV Core Protein p24; D007376:Interleukin-2; D016328:NF-kappa B; D010835:Phytohemagglutinins; D015375:Receptors, Interleukin-2; D013844:Thiazoles; D053778:Thiazolidines; D011761:Pyrrolidonecarboxylic Acid; C029536:2-oxothiazolidine-4-carboxylic acid