E5564 inhibits immunosuppressive cytokine IL-10 induction promoted by HIV-1 Tat protein

Virol J. 2014 Dec 4;11:214. doi: 10.1186/s12985-014-0214-z.

Abstract

Background: In HIV-1 infected patients, production of interleukin-10 (IL-10), a highly immunosuppressive cytokine, is associated with progression of infection toward AIDS. HIV-1 Tat protein, by interacting with TLR4-MD2 at the membrane level, induces IL-10 production by primary human monocytes and macrophages. In the present study we evaluated the effect of the TLR4 antagonist Eritoran tetrasodium (E5564) on HIV-1 Tat-induced IL-10 production.

Findings: Here, we confirm that the recombinant HIV-1 Tat protein and the GST-Tat 1-45 fusion protein efficiently stimulate IL-10 production by primary monocytes and macrophages and that this stimulation is inhibited by blocking anti-TLR4 mAbs. We show that a similar inhibition is observed by preincubating the cells with the TLR4 antagonist E5564.

Conclusion: This study provides compelling data showing for the first time that the TLR4 antagonist E5564 inhibits the immunosuppressive cytokine IL-10 production by primary human monocytes and macrophages incubated in the presence of HIV-1 Tat protein.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Gene Products, tat / metabolism*
  • HIV-1 / immunology*
  • Humans
  • Immunologic Factors / pharmacology*
  • Interleukin-10 / antagonists & inhibitors*
  • Lipid A / analogs & derivatives*
  • Lipid A / pharmacology
  • Macrophages / immunology
  • Macrophages / virology
  • Monocytes / immunology
  • Monocytes / virology
  • Toll-Like Receptor 4 / metabolism

Substances

  • E5564
  • Gene Products, tat
  • Immunologic Factors
  • Lipid A
  • TLR4 protein, human
  • Toll-Like Receptor 4
  • Interleukin-10