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The role of individual protein kinase C isoforms in mouse mast cell function and their targeting by the immunomodulatory parasitic worm product, ES-62

ES-62, a glycoprotein secreted by the filarial nematode Acanthocheilonema viteae, has been shown to modulate the immune system through subversion of signal transduction pathways operating in various immune system cells. With respect to human bone marrow-derived mast cells (BMMCs), ES-62 was previous...

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Autores principales: Bell, Kara S., Al-Riyami, Lamyaa, Lumb, Felicity E., Britton, Graham J., Poole, Alastair W., Williams, Christopher M., Braun, Ursula, Leitges, Michael, Harnett, Margaret M., Harnett, William
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier/North-Holland Biomedical Press 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4643489/
https://www.ncbi.nlm.nih.gov/pubmed/26343793
http://dx.doi.org/10.1016/j.imlet.2015.09.001
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author Bell, Kara S.
Al-Riyami, Lamyaa
Lumb, Felicity E.
Britton, Graham J.
Poole, Alastair W.
Williams, Christopher M.
Braun, Ursula
Leitges, Michael
Harnett, Margaret M.
Harnett, William
author_facet Bell, Kara S.
Al-Riyami, Lamyaa
Lumb, Felicity E.
Britton, Graham J.
Poole, Alastair W.
Williams, Christopher M.
Braun, Ursula
Leitges, Michael
Harnett, Margaret M.
Harnett, William
author_sort Bell, Kara S.
collection PubMed
description ES-62, a glycoprotein secreted by the filarial nematode Acanthocheilonema viteae, has been shown to modulate the immune system through subversion of signal transduction pathways operating in various immune system cells. With respect to human bone marrow-derived mast cells (BMMCs), ES-62 was previously shown to inhibit FcϵRI-mediated mast cell functional responses such as degranulation and pro-inflammatory cytokine release through a mechanism involving the degradation of PKC-α. At the same time, it was noted that the worm product was able to degrade certain other PKC isoforms but the significance of this was uncertain. In this study, we have employed PKC isoform KO mice to investigate the role of PKC-α, -β -ϵ, and -θ in mouse BMMCs in order to establish their involvement in mast cell-mediated responses and also, if their absence impacts on ES-62’s activity. The data obtained support that in response to antigen cross-linking of IgE bound to FcϵRI, pro-inflammatory cytokine release is controlled in part by a partnership between one conventional and one novel isoform with PKC-α and -θ acting as positive regulators of IL-6 and TNF-α production, while PKC-β and ϵ act as negative regulators of such cytokines. Furthermore, ES-62 appears to target certain other PKC isoforms in addition to PKC-α to inhibit cytokine release and this may enable it to more efficiently inhibit mast cell responses.
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spelling pubmed-46434892015-12-08 The role of individual protein kinase C isoforms in mouse mast cell function and their targeting by the immunomodulatory parasitic worm product, ES-62 Bell, Kara S. Al-Riyami, Lamyaa Lumb, Felicity E. Britton, Graham J. Poole, Alastair W. Williams, Christopher M. Braun, Ursula Leitges, Michael Harnett, Margaret M. Harnett, William Immunol Lett Article ES-62, a glycoprotein secreted by the filarial nematode Acanthocheilonema viteae, has been shown to modulate the immune system through subversion of signal transduction pathways operating in various immune system cells. With respect to human bone marrow-derived mast cells (BMMCs), ES-62 was previously shown to inhibit FcϵRI-mediated mast cell functional responses such as degranulation and pro-inflammatory cytokine release through a mechanism involving the degradation of PKC-α. At the same time, it was noted that the worm product was able to degrade certain other PKC isoforms but the significance of this was uncertain. In this study, we have employed PKC isoform KO mice to investigate the role of PKC-α, -β -ϵ, and -θ in mouse BMMCs in order to establish their involvement in mast cell-mediated responses and also, if their absence impacts on ES-62’s activity. The data obtained support that in response to antigen cross-linking of IgE bound to FcϵRI, pro-inflammatory cytokine release is controlled in part by a partnership between one conventional and one novel isoform with PKC-α and -θ acting as positive regulators of IL-6 and TNF-α production, while PKC-β and ϵ act as negative regulators of such cytokines. Furthermore, ES-62 appears to target certain other PKC isoforms in addition to PKC-α to inhibit cytokine release and this may enable it to more efficiently inhibit mast cell responses. Elsevier/North-Holland Biomedical Press 2015-11 /pmc/articles/PMC4643489/ /pubmed/26343793 http://dx.doi.org/10.1016/j.imlet.2015.09.001 Text en © 2015 The Authors http://creativecommons.org/licenses/by/4.0/ This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Bell, Kara S.
Al-Riyami, Lamyaa
Lumb, Felicity E.
Britton, Graham J.
Poole, Alastair W.
Williams, Christopher M.
Braun, Ursula
Leitges, Michael
Harnett, Margaret M.
Harnett, William
The role of individual protein kinase C isoforms in mouse mast cell function and their targeting by the immunomodulatory parasitic worm product, ES-62
title The role of individual protein kinase C isoforms in mouse mast cell function and their targeting by the immunomodulatory parasitic worm product, ES-62
title_full The role of individual protein kinase C isoforms in mouse mast cell function and their targeting by the immunomodulatory parasitic worm product, ES-62
title_fullStr The role of individual protein kinase C isoforms in mouse mast cell function and their targeting by the immunomodulatory parasitic worm product, ES-62
title_full_unstemmed The role of individual protein kinase C isoforms in mouse mast cell function and their targeting by the immunomodulatory parasitic worm product, ES-62
title_short The role of individual protein kinase C isoforms in mouse mast cell function and their targeting by the immunomodulatory parasitic worm product, ES-62
title_sort role of individual protein kinase c isoforms in mouse mast cell function and their targeting by the immunomodulatory parasitic worm product, es-62
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4643489/
https://www.ncbi.nlm.nih.gov/pubmed/26343793
http://dx.doi.org/10.1016/j.imlet.2015.09.001
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