Journal Article

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

Miossec, Pierre, Bartosch, Birke, Beringer, Audrey, Molle, Jennifer

2019

Overview

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.

• Publisher: Nature Publishing Group UK,Nature Publishing Group
• Subject: 13/106 / 13/21 / 13/31 / 631/250/127 / 692/308/575 / Carcinoma, Hepatocellular - genetics / Carcinoma, Hepatocellular - pathology / CD3 antigen / CD4 antigen / Cell Behavior / Cell Communication - genetics / Cell culture / Cell interactions / Cell Line, Tumor / Cell proliferation / Cellular Biology / Chemokine CCL2 - genetics / Chemokines / Coculture Techniques / Cytokines / Fibroblasts / Gene expression / Gene Expression Regulation, Neoplastic / Hepatitis / Hepatocytes / Hepatocytes - metabolism / Hepatocytes - pathology / Hepatoma / Histocompatibility antigen HLA / Human health and pathology / Humanities and Social Sciences / Humans / Hépatology and Gastroenterology / Immune response / Immunological tolerance / Immunology / Inflammation / Inflammation - genetics / Inflammation - pathology / Innate immunity / Interleukin 17 / Interleukin 6 / Interleukin 8 / Interleukin-17 - genetics / Interleukin-6 - genetics / Interleukin-8 - genetics / Kinetics / Leukocytes (mononuclear) / Leukocytes, Mononuclear - metabolism / Leukocytes, Mononuclear - pathology / Life Sciences / Liver / Liver - metabolism / Liver - pathology / Liver cancer / Liver diseases / Liver Neoplasms - genetics / Liver Neoplasms - pathology / Lymphocytes T / Monocyte chemoattractant protein 1 / multidisciplinary / Peripheral blood mononuclear cells / RNA, Messenger - genetics / Science / Science (multidisciplinary) / Skin / Tumor Necrosis Factor-alpha - genetics / Tumor necrosis factor-α