Inorganic arsenic alters expression of immune and stress response genes in activated primary human T lymphocytes

Autor: Marie-Dominique Galibert, Olivier Fardel, Mélodie Bonvalet, Laurent Vernhet, Corinne Martin-Chouly, Claudie Morzadec
Přispěvatelé: De Villemeur, Hervé, Signalisation et Réponses aux Agents Infectieux et Chimiques (SeRAIC), Université de Rennes (UR), Institut de Génétique et Développement de Rennes (IGDR), Université de Rennes (UR)-Centre National de la Recherche Scientifique (CNRS), Service d'Hématologie, Immunologie et de Thérapie Cellulaire (HITC), Université de Rennes (UR)-Hôpital Pontchaillou-CHU Pontchaillou [Rennes], Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Centre National de la Recherche Scientifique (CNRS), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou-CHU Pontchaillou [Rennes], Centre National de la Recherche Scientifique (CNRS)-Université de Rennes 1 (UR1)
Rok vydání: 2011
Předmět:
MESH: Signal Transduction
MESH: Tissue Donors
Time Factors
Sodium arsenite
T-Lymphocytes
Cell Separation
Lymphocyte Activation
chemistry.chemical_compound
0302 clinical medicine
MESH: Up-Regulation
Immunotoxicity
Lymphocytes
MESH: Sodium Compounds
IL-2 receptor
MESH: Stress
Physiological
Receptor
Cells
Cultured
MESH: Immunity
Oligonucleotide Array Sequence Analysis
0303 health sciences
MESH: Heme Oxygenase-1
Sodium Compounds
MESH: Gene Expression Regulation
Tissue Donors
Up-Regulation
3. Good health
medicine.anatomical_structure
Biochemistry
030220 oncology & carcinogenesis
[SDV.IMM]Life Sciences [q-bio]/Immunology
Tumor necrosis factor alpha
MESH: Arsenites
Signal Transduction
MESH: Cells
Cultured
medicine.drug
Interleukin 2
[SDV.IMM] Life Sciences [q-bio]/Immunology
Arsenites
T cell
Immunology
Biology
MESH: Cell Separation
Peripheral blood mononuclear cell
MESH: Phytohemagglutinins
MESH: Receptors
Interleukin-2
03 medical and health sciences
Immune system
Stress
Physiological
medicine
Humans
Phytohemagglutinins
MESH: Lymphocyte Activation
Molecular Biology
030304 developmental biology
MESH: Humans
Inorganic arsenic
MESH: Time Factors
Immunity
Receptors
Interleukin-2
MESH: Interleukin-2
Molecular biology
Heme-oxygenase 1
MESH: T-Lymphocytes
Gene Expression Regulation
chemistry
MESH: Oligonucleotide Array Sequence Analysis
Interleukin-2
Heme Oxygenase-1
Zdroj: Molecular Immunology
Molecular Immunology, 2011, 48 (6-7), pp.956-65. ⟨10.1016/j.molimm.2011.01.005⟩
Molecular Immunology, Elsevier, 2011, 48 (6-7), pp.956-65. ⟨10.1016/j.molimm.2011.01.005⟩
ISSN: 0161-5890
DOI: 10.1016/j.molimm.2011.01.005
Popis: International audience; Inorganic arsenic, a carcinogenic environmental contaminant, exerts immunosuppressive effects on human T lymphocytes. In particular, interleukin-2 (IL2) secretion and T cell proliferation are reduced when peripheral blood mononuclear cells (PBMC) from individuals chronically exposed to arsenic are stimulated ex vivo with lectins such as phytohemaglutinin (PHA). However, it is not clear whether the metalloid directly acts on T cells or blocks monocyte-dependent accessory signals activated by PHA. We report that in vitro pre-treatment of PBMC with sodium arsenite (NaAs) reduces IL2 secretion and T cell proliferation induced by PHA, but does not prevent expression of monocyte-derived cytokines (IL1, IL6, TNFα) functioning as lymphocyte-activating factors. In addition, we found that NaAs delays induction of IL2 and IL2 receptor α chain (IL2RA) mRNA levels in human primary isolated T cells activated by PHA. Kinetic analysis showed that NaAs pre-treatment first inhibits, but thereafter markedly increases, induction of IL2 and IL2RA mRNA when T cells are stimulated with PHA for 8 h and 72 h, respectively. We conducted whole genome microarray-based analysis of gene expression in primary T cell cultures derived from independent donors. NaAs systematically and significantly up-regulated a set of 35 genes, including several immune and stress genes, such as IL13, granulocyte-macrophage colony stimulating factor, lymphotoxin α and heme oxygenase-1 (HO-1). Up-regulation of HO-1, a stress and immunosuppressive protein, was rapidly detectable, both in T cells and in PBMC treated with NaAs. Inhibition of the immunosuppressive activity of HO-1 in PBMC however failed to prevent NaAs-dependent inhibition of T cell proliferation induced by PHA. Our findings demonstrate that, at least in vitro, inorganic arsenic acts directly on human T cells and impairs their activity, probably independently of HO-1 expression and monocyte-related accessory signals.
Databáze: OpenAIRE
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