Inhibitors of histone deacetylases impair innate immune responses of macrophages : P215

Détails

ID Serval
serval:BIB_8F2C57277CB6
Type
Actes de conférence (partie): contribution originale à la littérature scientifique, publiée à l'occasion de conférences scientifiques, dans un ouvrage de compte-rendu (proceedings), ou dans l'édition spéciale d'un journal reconnu (conference proceedings).
Sous-type
Poster: résume de manière illustrée et sur une page unique les résultats d'un projet de recherche. Les résumés de poster doivent être entrés sous "Abstract" et non "Poster".
Collection
Publications
Titre
Inhibitors of histone deacetylases impair innate immune responses of macrophages : P215
Titre de la conférence
Annual Joint Meeting of the Swiss Societies for Pneumology, Paediatric Pneumology, Allergology and Immunology, Thoracic Surgery
Auteur(s)
Mombelli M., Francois P., Giddey M., Reymond M.K., Lugrin J., Schrenzel J., Calandra T., Roger T.
Adresse
Fribourg, April 17 and 18, 2008
ISBN
1424-7860
Statut éditorial
Publié
Date de publication
2008
Peer-reviewed
Oui
Volume
138
Série
Swiss Medical Weekly
Pages
49S-50S
Langue
anglais
Notes
Background: Histone deacetylases are regulators of chromatin structure and gene expression. Originally investigated as anticancer drugs, histone deacetylases inhibitors (HDI) have emerged to be potent anti-inflammatory agents for auto-immune, allergic and inflammatory diseases. Yet, the influence of HDIs on innate immune responses remains scarcely studied.
Objective: To investigate the influence of HDIs on the generation of cytokines and reactive oxygen and nitrogen species (ROS et NO), the phagocytosis and the killing by murine bone-marrow derived macrophages (BMDMs) exposed to microbial products.
Methods: BMDMs were pre-incubated (1, 4, 8 or 14 h) with the HDIs trichostatin A (TSA), sodium butyrate (NaB) or valproic acid (VPA) before exposure to LPS, Pam3CSK4, IFNg, LPS+IFNg, E. coli, S. aureus and phorbol myristate acetate (PMA). Cytokines, ROS and NO were measured by bioassay and ELISA and using DCFDA and the Griess reagent, respectively. Gene expression was analyzed using Agilent high density DNA arrays and confirmed for selected genes by real-time PCR. Inducible NO synthase (iNOS) protein levels were quantified by Western blotting. E. coli and S. aureus phagocytosis and killing were quantified by conventional methods.
Results: TSA, NaB and VPA dose-dependently inhibited TNF, IL-6 and IL-12 release by BMDMs exposed to bacterial products. HDIs also reduced ROS production induced by PMA and NO production induced by PMA, LPS, LPS+IFNg and bacteria. In agreement with these observations, HDIs strongly hampered basal expression and/or
stimulus-induced upregulation of p22, p40, p47, p67 and p91 phox mRNA and iNOS mRNA and protein expression in BMDMs. Finally, the phagocytosis and the killing of E. coli and S. aureus were strongly
reduced in BMDMs pre-incubated with TSA and VPA.
Conclusions: HDIs exhibit profound inhibitory effects on innate immune functions of macrophages. These results suggest that HDIs might impair innate immune defenses and thus predispose patients, especially immunocompromised patients, who are treated with these agent to severe infections.
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Création de la notice
13/10/2009 14:20
Dernière modification de la notice
03/03/2018 19:21
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