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

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

Author information

1
Université Paul Sabatier, EA 3038, 118 Route de Narbonne, 31062, Toulouse, France. bahraoui@cict.fr.
2
INSERM, U1043, CPTP, CHU Purpan, BP3028, 31024, Toulouse, Cedex 3, France. bahraoui@cict.fr.
3
CNRS, U5282, CPTP, CHU Purpan, BP3028, 31024, Toulouse, Cedex3, France. bahraoui@cict.fr.
4
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.
5
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.

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.

PMID:
25471526
PMCID:
PMC4267154
DOI:
10.1186/s12985-014-0214-z
[Indexed for MEDLINE]
Free PMC Article

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