Inhibitors of histone deacetylases impair innate immune responses of macrophages : P215
Details
Serval ID
serval:BIB_8F2C57277CB6
Type
Inproceedings: an article in a conference proceedings.
Publication sub-type
Poster: Summary – with images – on one page of the results of a researche project. The summaries of the poster must be entered in "Abstract" and not "Poster".
Collection
Publications
Institution
Title
Inhibitors of histone deacetylases impair innate immune responses of macrophages : P215
Title of the conference
Annual Joint Meeting of the Swiss Societies for Pneumology, Paediatric Pneumology, Allergology and Immunology, Thoracic Surgery
Address
Fribourg, April 17 and 18, 2008
ISBN
1424-7860
Publication state
Published
Issued date
2008
Peer-reviewed
Oui
Volume
138
Series
Swiss Medical Weekly
Pages
49S-50S
Language
english
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.
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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Create date
13/10/2009 14:20
Last modification date
20/08/2019 15:52
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