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Two phase kinetics of the inflammatory response from hepatocyte-peripheral blood mononuclear cell interactions

Active liver diseases are characterized by an infiltration of inflammatory immune cells, which interact locally with hepatocytes. Co-cultures between non- and -activated human peripheral blood mononuclear cells (PBMCs) and human hepatoma HepaRG cells were used to determine the role of these cell int...

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Autores principales: Beringer, Audrey, Molle, Jennifer, Bartosch, Birke, Miossec, Pierre
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6557861/
https://www.ncbi.nlm.nih.gov/pubmed/31182764
http://dx.doi.org/10.1038/s41598-019-44840-w
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author Beringer, Audrey
Molle, Jennifer
Bartosch, Birke
Miossec, Pierre
author_facet Beringer, Audrey
Molle, Jennifer
Bartosch, Birke
Miossec, Pierre
author_sort Beringer, Audrey
collection PubMed
description Active liver diseases are characterized by an infiltration of inflammatory immune cells, which interact locally with hepatocytes. Co-cultures between non- and -activated human peripheral blood mononuclear cells (PBMCs) and human hepatoma HepaRG cells were used to determine the role of these cell interactions in the inflammatory response. At the early stage, PBMC-HepaRG cell interactions increased mRNA expression and/or secretion of IL-6, IL-8, CCL-20 and MCP-1, in part through direct cell contact and the induction was higher in PHA-activated conditions. The pro-inflammatory cytokines IL-17 and/or TNFα contributed to the increase of IL-6 and IL-8 secretion. HepaRG cells modulated T cell polarization by increasing Th1 cell transcription factor expression and by reducing CD3(+) CD4(+) IL-17(+) cell frequency when PBMCs were activated with PHA. At a later stage, the presence of HepaRG cells inhibited PHA-induced HLA-DR expression on PBMCs, and PBMC proliferation. In contrast, the presence of skin fibroblasts had no effect of PBMC proliferation induced by PHA. After a first pro-inflammatory phase, PBMC-HepaRG cell interactions may down-regulate the immune response. The PBMC-hepatocyte interactions can thus participate first to the initiation of hepatitis and later to the maintenance of immune tolerance in liver, possibly contributing to chronicity.
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spelling pubmed-65578612019-06-19 Two phase kinetics of the inflammatory response from hepatocyte-peripheral blood mononuclear cell interactions Beringer, Audrey Molle, Jennifer Bartosch, Birke Miossec, Pierre Sci Rep Article Active liver diseases are characterized by an infiltration of inflammatory immune cells, which interact locally with hepatocytes. Co-cultures between non- and -activated human peripheral blood mononuclear cells (PBMCs) and human hepatoma HepaRG cells were used to determine the role of these cell interactions in the inflammatory response. At the early stage, PBMC-HepaRG cell interactions increased mRNA expression and/or secretion of IL-6, IL-8, CCL-20 and MCP-1, in part through direct cell contact and the induction was higher in PHA-activated conditions. The pro-inflammatory cytokines IL-17 and/or TNFα contributed to the increase of IL-6 and IL-8 secretion. HepaRG cells modulated T cell polarization by increasing Th1 cell transcription factor expression and by reducing CD3(+) CD4(+) IL-17(+) cell frequency when PBMCs were activated with PHA. At a later stage, the presence of HepaRG cells inhibited PHA-induced HLA-DR expression on PBMCs, and PBMC proliferation. In contrast, the presence of skin fibroblasts had no effect of PBMC proliferation induced by PHA. After a first pro-inflammatory phase, PBMC-HepaRG cell interactions may down-regulate the immune response. The PBMC-hepatocyte interactions can thus participate first to the initiation of hepatitis and later to the maintenance of immune tolerance in liver, possibly contributing to chronicity. Nature Publishing Group UK 2019-06-10 /pmc/articles/PMC6557861/ /pubmed/31182764 http://dx.doi.org/10.1038/s41598-019-44840-w Text en © The Author(s) 2019 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Beringer, Audrey
Molle, Jennifer
Bartosch, Birke
Miossec, Pierre
Two phase kinetics of the inflammatory response from hepatocyte-peripheral blood mononuclear cell interactions
title Two phase kinetics of the inflammatory response from hepatocyte-peripheral blood mononuclear cell interactions
title_full Two phase kinetics of the inflammatory response from hepatocyte-peripheral blood mononuclear cell interactions
title_fullStr Two phase kinetics of the inflammatory response from hepatocyte-peripheral blood mononuclear cell interactions
title_full_unstemmed Two phase kinetics of the inflammatory response from hepatocyte-peripheral blood mononuclear cell interactions
title_short Two phase kinetics of the inflammatory response from hepatocyte-peripheral blood mononuclear cell interactions
title_sort two phase kinetics of the inflammatory response from hepatocyte-peripheral blood mononuclear cell interactions
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6557861/
https://www.ncbi.nlm.nih.gov/pubmed/31182764
http://dx.doi.org/10.1038/s41598-019-44840-w
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