Prostaglandin E2 increases bovine leukemia virus tax and pol mRNA levels via cyclooxygenase 2: Regulation by interleukin-2, interleukin-10, and bovine leukemia virus

Dohun Pyeon, Francisco J. Diaz, Gary A. Splitter

Research output: Contribution to journalArticle

45 Scopus citations

Abstract

Prostaglandin E2 (PGE2), 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 PGE2, 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 PGE2 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 PGE2 increased BLV tax mRNA regardless of NS-398 addition. PGE2 inhibited antigen-specific PBMC stimulation, suggesting that stimulation of BLV tax and pol mRNA levels by PGE2 is independent of cell proliferation. These findings suggest that macrophage-derived COX-2 products, such as PGE2, regulate virus expression and disease progression in BLV infection.

Original languageEnglish (US)
Pages (from-to)5740-5745
Number of pages6
JournalJournal of virology
Volume74
Issue number12
DOIs
StatePublished - Jun 22 2000

All Science Journal Classification (ASJC) codes

  • Microbiology
  • Immunology
  • Insect Science
  • Virology

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