prostaglandin-a2 and ciglitazone

Previous studies have demonstrated that cyclopentenone prostaglandins (cyPG) inhibit human immunodeficiency virus type 1 (HIV-1) replication in various cell types. We investigated the role of PG in the replication of HIV-1 in primary macrophages. The cyPG, PGA(1) and PGA(2), inhibited HIV-1 replication in acutely infected human monocyte-derived macrophages (MDM). Because PGA(1) and PGA(2) have previously been shown to be peroxisome proliferator-activated receptor gamma (PPARgamma) agonists, we examined the effect of synthetic PPARgamma agonists on HIV replication. The PPARgamma agonist ciglitazone inhibited HIV-1 replication in a dose-dependent manner in acutely infected human MDM. In addition, cyPG and ciglitazone reduced HIV replication in latently infected and viral entry-independent U1 cells, suggesting an effect at the level of HIV gene expression. Ciglitazone also suppressed HIV-1 mRNA levels as measured by reverse transcriptase PCR, in parallel with the decrease in reverse transcriptase activity. Co-transfection of PPARgamma wild type vectors and treatment with PPARgamma agonists inhibited HIV-1 promoter activity in U937 cells. Activation of PPARgamma also decreased HIV-1 mRNA stability following actinomycin D treatment. In summary, our experimental findings implicate PPARgamma as an important factor in the suppression of HIV-1 gene expression in MDM by cyPG. Thus natural and synthetic PPARgamma agonists may play a role in controlling HIV-1 infection in macrophages.

Topics: Cell Line; Cells, Cultured; Dactinomycin; Dose-Response Relationship, Drug; HeLa Cells; HIV-1; Humans; Hypoglycemic Agents; Macrophages; Plasmids; Promoter Regions, Genetic; Prostaglandins A; Protein Synthesis Inhibitors; Receptors, Cytoplasmic and Nuclear; Reverse Transcriptase Polymerase Chain Reaction; RNA Processing, Post-Transcriptional; RNA-Directed DNA Polymerase; RNA, Messenger; Thiazoles; Thiazolidinediones; Time Factors; Transcription Factors; Transcription, Genetic; Transfection; U937 Cells