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

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 m...

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Autores principales: Bahraoui, Elmostafa, Briant, Laurence, Chazal, Nathalie
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4267154/
https://www.ncbi.nlm.nih.gov/pubmed/25471526
http://dx.doi.org/10.1186/s12985-014-0214-z
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author Bahraoui, Elmostafa
Briant, Laurence
Chazal, Nathalie
author_facet Bahraoui, Elmostafa
Briant, Laurence
Chazal, Nathalie
author_sort Bahraoui, Elmostafa
collection PubMed
description 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.
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spelling pubmed-42671542014-12-17 E5564 inhibits immunosuppressive cytokine IL-10 induction promoted by HIV-1 Tat protein Bahraoui, Elmostafa Briant, Laurence Chazal, Nathalie Virol J Short Report 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. BioMed Central 2014-12-04 /pmc/articles/PMC4267154/ /pubmed/25471526 http://dx.doi.org/10.1186/s12985-014-0214-z Text en © Bahraoui et al.; licensee BioMed Central Ltd. 2014 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Short Report
Bahraoui, Elmostafa
Briant, Laurence
Chazal, Nathalie
E5564 inhibits immunosuppressive cytokine IL-10 induction promoted by HIV-1 Tat protein
title E5564 inhibits immunosuppressive cytokine IL-10 induction promoted by HIV-1 Tat protein
title_full E5564 inhibits immunosuppressive cytokine IL-10 induction promoted by HIV-1 Tat protein
title_fullStr E5564 inhibits immunosuppressive cytokine IL-10 induction promoted by HIV-1 Tat protein
title_full_unstemmed E5564 inhibits immunosuppressive cytokine IL-10 induction promoted by HIV-1 Tat protein
title_short E5564 inhibits immunosuppressive cytokine IL-10 induction promoted by HIV-1 Tat protein
title_sort e5564 inhibits immunosuppressive cytokine il-10 induction promoted by hiv-1 tat protein
topic Short Report
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4267154/
https://www.ncbi.nlm.nih.gov/pubmed/25471526
http://dx.doi.org/10.1186/s12985-014-0214-z
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