title: Prostaglandin E(2) increases bovine leukemia virus tax and pol mRNA levels via cyclooxygenase 2: regulation by interleukin-2, interleukin-10, and bovine leukemia virus.
abstract: Prostaglandin E(2) (PGE(2)), produced by macrophages, has important immune regulatory functions, suppressing a type 1 immune response and stimulating a type 2 immune response. Type 1 cytokines (interleukin-2 [IL-2], IL-12, and gamma interferon) increase in freshly isolated peripheral blood mononuclear cells (PBMCs) of animals with an early disease stage of bovine leukemia virus (BLV) infection, while IL-10 increases in animals with a late disease stage. Although IL-10 has an immunosuppressive role in the host immune system, IL-10 also inhibits BLV tax and pol mRNA levels in vitro. In contrast, IL-2 stimulates BLV tax and pol mRNA and p24 protein expression in cultured PBMCs. The inhibitory effect of IL-10 on BLV expression depends on soluble factors secreted by macrophages. Thus, we hypothesized that PGE(2), a cyclooxygenase 2 (COX-2) product of macrophages, may regulate BLV expression. Here, we show that the level of COX-2 mRNA was decreased in PBMCs treated with IL-10, while IL-2 enhanced the level of COX-2 mRNA. Addition of PGE(2) stimulated BLV tax and pol mRNA levels and reversed the IL-10 inhibition of BLV mRNA. In addition, the specific COX-2 inhibitor, NS-398, inhibited the amount of BLV mRNA detected. Addition of PGE(2) increased BLV tax mRNA regardless of NS-398 addition. PGE(2) inhibited antigen-specific PBMC stimulation, suggesting that stimulation of BLV tax and pol mRNA levels by PGE(2) is independent of cell proliferation. These findings suggest that macrophage-derived COX-2 products, such as PGE(2), regulate virus expression and disease progression in BLV infection.
authors.affiliation: Department of Animal Health and Biomedical Sciences, University of Wisconsin-Madison, Madison, Wisconsin 53706, USA.
authors.forename: D
authors.initials: D
authors.lastname: Pyeon
authors.forename: F J
authors.initials: FJ
authors.lastname: Diaz
authors.forename: G A
authors.initials: GA
authors.lastname: Splitter
mesh_terms: D000818:Animals; D019898:Autocrine Communication; D002417:Cattle; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D015232:Dinoprostone / Q000494:pharmacology*; D015967:Gene Expression Regulation, Viral / Q000187:drug effects; D015684:Gene Products, pol / Q000235:genetics*; D016356:Gene Products, tax / Q000235:genetics*; D016753:Interleukin-10 / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D007376:Interleukin-2 / Q000494:pharmacology*; D007527:Isoenzymes / Q000235:genetics* / Q000378:metabolism / Q000494:pharmacology; D001909:Leukemia Virus, Bovine / Q000187:drug effects* / Q000235:genetics / Q000276:immunology / Q000502:physiology; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000201:enzymology / Q000276:immunology / Q000821:virology; D008213:Lymphocyte Activation / Q000187:drug effects; D008954:Models, Biological; D009578:Nitrobenzenes / Q000494:pharmacology; D011451:Prostaglandin-Endoperoxide Synthases / Q000235:genetics* / Q000378:metabolism / Q000494:pharmacology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012367:RNA, Viral / Q000235:genetics / Q000378:metabolism; D013449:Sulfonamides / Q000494:pharmacology
chemical_list: D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D015684:Gene Products, pol; D016356:Gene Products, tax; D007376:Interleukin-2; D007527:Isoenzymes; D009578:Nitrobenzenes; D012333:RNA, Messenger; D012367:RNA, Viral; D013449:Sulfonamides; C080955:N-(2-cyclohexyloxy-4-nitrophenyl)methanesulfonamide; D016753:Interleukin-10; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases; D015232:Dinoprostone