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Therapeutic Efficacy and Immunological Response of CCL5 Antagonists in Models of Contact Skin Reaction

Skin-infiltrating T-cells play a predominant role in allergic and inflammatory skin diseases such as atopic dermatitis, psoriasis and allergic contact dermatitis. These T-cells are attracted by several chemotactic factors including the chemokine CCL5/RANTES, a CC chemokine inducing both the migratio...

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Autores principales: Canavese, Miriam, Altruda, Fiorella, Silengo, Lorenzo
Formato: Texto
Lenguaje:English
Publicado: Public Library of Science 2010
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2806914/
https://www.ncbi.nlm.nih.gov/pubmed/20090949
http://dx.doi.org/10.1371/journal.pone.0008725
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author Canavese, Miriam
Altruda, Fiorella
Silengo, Lorenzo
author_facet Canavese, Miriam
Altruda, Fiorella
Silengo, Lorenzo
author_sort Canavese, Miriam
collection PubMed
description Skin-infiltrating T-cells play a predominant role in allergic and inflammatory skin diseases such as atopic dermatitis, psoriasis and allergic contact dermatitis. These T-cells are attracted by several chemotactic factors including the chemokine CCL5/RANTES, a CC chemokine inducing both the migration and activation of specific leukocyte subsets. CCL5 has been found to be associated with various cell-mediated hypersensitive disorders such as psoriasis, atopic dermatitis and irritant contact dermatitis. We have used two antagonists, the first, Met-CCL5, a dual CCR1/CCR5 antagonist and the second, a variant in which GAG binding is abrogated, (44)AANA(47)-CCL5, which acts as a dominant negative inhibitor of CCL5. The antagonists were tested in two models of contact skin reaction. The first, irritant contact dermatitis (ICD) is a pathological non-specific inflammatory skin condition arising from the release of pro-inflammatory cytokines by keratinocytes in response to haptens, usually chemicals. The second, contact hypersensitivity (CHS) is a T-cell dependent model, mimicking in part the T-cell-mediated skin diseases such as psoriasis. In both models, the CCL5 antagonists showed therapeutic efficacy by reducing swelling by 50% as well as the reduction of soluble mediators in homogenates derived from challenged ears. These results demonstrate that blocking the receptor or the ligand are both effective strategies to inhibit skin inflammation.
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spelling pubmed-28069142010-01-21 Therapeutic Efficacy and Immunological Response of CCL5 Antagonists in Models of Contact Skin Reaction Canavese, Miriam Altruda, Fiorella Silengo, Lorenzo PLoS One Research Article Skin-infiltrating T-cells play a predominant role in allergic and inflammatory skin diseases such as atopic dermatitis, psoriasis and allergic contact dermatitis. These T-cells are attracted by several chemotactic factors including the chemokine CCL5/RANTES, a CC chemokine inducing both the migration and activation of specific leukocyte subsets. CCL5 has been found to be associated with various cell-mediated hypersensitive disorders such as psoriasis, atopic dermatitis and irritant contact dermatitis. We have used two antagonists, the first, Met-CCL5, a dual CCR1/CCR5 antagonist and the second, a variant in which GAG binding is abrogated, (44)AANA(47)-CCL5, which acts as a dominant negative inhibitor of CCL5. The antagonists were tested in two models of contact skin reaction. The first, irritant contact dermatitis (ICD) is a pathological non-specific inflammatory skin condition arising from the release of pro-inflammatory cytokines by keratinocytes in response to haptens, usually chemicals. The second, contact hypersensitivity (CHS) is a T-cell dependent model, mimicking in part the T-cell-mediated skin diseases such as psoriasis. In both models, the CCL5 antagonists showed therapeutic efficacy by reducing swelling by 50% as well as the reduction of soluble mediators in homogenates derived from challenged ears. These results demonstrate that blocking the receptor or the ligand are both effective strategies to inhibit skin inflammation. Public Library of Science 2010-01-15 /pmc/articles/PMC2806914/ /pubmed/20090949 http://dx.doi.org/10.1371/journal.pone.0008725 Text en Canavese et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Canavese, Miriam
Altruda, Fiorella
Silengo, Lorenzo
Therapeutic Efficacy and Immunological Response of CCL5 Antagonists in Models of Contact Skin Reaction
title Therapeutic Efficacy and Immunological Response of CCL5 Antagonists in Models of Contact Skin Reaction
title_full Therapeutic Efficacy and Immunological Response of CCL5 Antagonists in Models of Contact Skin Reaction
title_fullStr Therapeutic Efficacy and Immunological Response of CCL5 Antagonists in Models of Contact Skin Reaction
title_full_unstemmed Therapeutic Efficacy and Immunological Response of CCL5 Antagonists in Models of Contact Skin Reaction
title_short Therapeutic Efficacy and Immunological Response of CCL5 Antagonists in Models of Contact Skin Reaction
title_sort therapeutic efficacy and immunological response of ccl5 antagonists in models of contact skin reaction
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2806914/
https://www.ncbi.nlm.nih.gov/pubmed/20090949
http://dx.doi.org/10.1371/journal.pone.0008725
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