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TSG-6 Downregulates IFN-Alpha and TNF-Alpha Expression by Suppressing IRF7 Phosphorylation in Human Plasmacytoid Dendritic Cells

Proinflammatory cytokines such as TNF-α and type I interferons (IFN) are pathogenic signatures of systemic lupus erythematosus, and plasmacytoid dendritic cells (pDCs) play a major role by predominantly producing IFN-α. Given the rise of importance in identifying tumor necrosis stimulated gene 6 (TS...

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Detalles Bibliográficos
Autores principales: Kui, L., Chan, G. C., Lee, P. P. W.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Hindawi 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5358455/
https://www.ncbi.nlm.nih.gov/pubmed/28367002
http://dx.doi.org/10.1155/2017/7462945
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author Kui, L.
Chan, G. C.
Lee, P. P. W.
author_facet Kui, L.
Chan, G. C.
Lee, P. P. W.
author_sort Kui, L.
collection PubMed
description Proinflammatory cytokines such as TNF-α and type I interferons (IFN) are pathogenic signatures of systemic lupus erythematosus, and plasmacytoid dendritic cells (pDCs) play a major role by predominantly producing IFN-α. Given the rise of importance in identifying tumor necrosis stimulated gene 6 (TSG-6) as a key anti-inflammatory regulator, we investigate its function and its ability to counteract proinflammatory cytokine secretion by pDCs in vitro. CpG-A and R837 induced significant endogenous TSG-6 expression in the pDC cell-line GEN2.2. Following recombinant human TSG-6 treatment and CpG-A or R837 stimulation, significant reduction in IFN-α and TNF-α was observed in healthy donors' pDCs, and the same phenomenon was confirmed in GEN2.2. By CD44 blocking assay, we deduced that the suppressive effect of TSG-6 is mediated by CD44, by reducing IRF-7 phosphorylation. Our findings suggest that TSG-6 and its downstream signalling pathway could potentially be targeted to modulate proinflammatory cytokine expression in pDCs.
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spelling pubmed-53584552017-04-02 TSG-6 Downregulates IFN-Alpha and TNF-Alpha Expression by Suppressing IRF7 Phosphorylation in Human Plasmacytoid Dendritic Cells Kui, L. Chan, G. C. Lee, P. P. W. Mediators Inflamm Research Article Proinflammatory cytokines such as TNF-α and type I interferons (IFN) are pathogenic signatures of systemic lupus erythematosus, and plasmacytoid dendritic cells (pDCs) play a major role by predominantly producing IFN-α. Given the rise of importance in identifying tumor necrosis stimulated gene 6 (TSG-6) as a key anti-inflammatory regulator, we investigate its function and its ability to counteract proinflammatory cytokine secretion by pDCs in vitro. CpG-A and R837 induced significant endogenous TSG-6 expression in the pDC cell-line GEN2.2. Following recombinant human TSG-6 treatment and CpG-A or R837 stimulation, significant reduction in IFN-α and TNF-α was observed in healthy donors' pDCs, and the same phenomenon was confirmed in GEN2.2. By CD44 blocking assay, we deduced that the suppressive effect of TSG-6 is mediated by CD44, by reducing IRF-7 phosphorylation. Our findings suggest that TSG-6 and its downstream signalling pathway could potentially be targeted to modulate proinflammatory cytokine expression in pDCs. Hindawi 2017 2017-03-06 /pmc/articles/PMC5358455/ /pubmed/28367002 http://dx.doi.org/10.1155/2017/7462945 Text en Copyright © 2017 L. Kui et al. https://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Kui, L.
Chan, G. C.
Lee, P. P. W.
TSG-6 Downregulates IFN-Alpha and TNF-Alpha Expression by Suppressing IRF7 Phosphorylation in Human Plasmacytoid Dendritic Cells
title TSG-6 Downregulates IFN-Alpha and TNF-Alpha Expression by Suppressing IRF7 Phosphorylation in Human Plasmacytoid Dendritic Cells
title_full TSG-6 Downregulates IFN-Alpha and TNF-Alpha Expression by Suppressing IRF7 Phosphorylation in Human Plasmacytoid Dendritic Cells
title_fullStr TSG-6 Downregulates IFN-Alpha and TNF-Alpha Expression by Suppressing IRF7 Phosphorylation in Human Plasmacytoid Dendritic Cells
title_full_unstemmed TSG-6 Downregulates IFN-Alpha and TNF-Alpha Expression by Suppressing IRF7 Phosphorylation in Human Plasmacytoid Dendritic Cells
title_short TSG-6 Downregulates IFN-Alpha and TNF-Alpha Expression by Suppressing IRF7 Phosphorylation in Human Plasmacytoid Dendritic Cells
title_sort tsg-6 downregulates ifn-alpha and tnf-alpha expression by suppressing irf7 phosphorylation in human plasmacytoid dendritic cells
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5358455/
https://www.ncbi.nlm.nih.gov/pubmed/28367002
http://dx.doi.org/10.1155/2017/7462945
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