title: E5564 inhibits immunosuppressive cytokine IL-10 induction promoted by HIV-1 Tat protein.
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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Université Paul Sabatier, EA 3038, 118 Route de Narbonne, 31062, Toulouse, France. bahraoui@cict.fr.|INSERM, U1043, CPTP, CHU Purpan, BP3028, 31024, Toulouse, Cedex 3, France. bahraoui@cict.fr.|CNRS, U5282, CPTP, CHU Purpan, BP3028, 31024, Toulouse, Cedex3, France. bahraoui@cict.fr.
authors.forename: Elmostafa
authors.initials: E
authors.lastname: Bahraoui
authors.affiliation: Centre d'études d'agents Pathogènes et Biotechnologies pour la Santé (CPBS), UMR5236, CNRS - Université Montpellier 1-Montpellier 2, Montpellier, France. laurence.briant@cpbs.cnrs.fr.
authors.forename: Laurence
authors.initials: L
authors.lastname: Briant
authors.affiliation: Centre d'études d'agents Pathogènes et Biotechnologies pour la Santé (CPBS), UMR5236, CNRS - Université Montpellier 1-Montpellier 2, Montpellier, France. nathalie.chazal@cpbs.cnrs.fr.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Chazal
mesh_terms: D015696:Gene Products, tat / Q000378:metabolism*; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D007155:Immunologic Factors / Q000494:pharmacology*; D016753:Interleukin-10 / Q000037:antagonists & inhibitors*; D008050:Lipid A / Q000031:analogs & derivatives* / Q000494:pharmacology; D008264:Macrophages / Q000276:immunology / Q000821:virology; D009000:Monocytes / Q000276:immunology / Q000821:virology; D051197:Toll-Like Receptor 4 / Q000378:metabolism
chemical_list: C404742:E5564; D015696:Gene Products, tat; D007155:Immunologic Factors; D008050:Lipid A; C495345:TLR4 protein, human; D051197:Toll-Like Receptor 4; D016753:Interleukin-10