Sirtuin inhibition attenuates the production of inflammatory cytokines in lipopolysaccharide-stimulated macrophages.

Animals; Cell Line; Chemokine CCL5/biosynthesis; Cytokines/biosynthesis; Histone Deacetylase Inhibitors/pharmacology; Inflammation/enzymology/immunology; Interleukin-6/metabolism; Lipopolysaccharides/immunology; Macrophages/enzymology/immunology; Mice; Mitogen-Activated Protein Kinase Kinases/metabolism; NF-kappa B/metabolism; Naphthalenes/pharmacology; Phosphorylation/drug effects; Pyrimidinones/pharmacology; Sirtuins/antagonists & inhibitors/metabolism; Tumor Necrosis Factor-alpha/metabolism

Abstract :

[en] In several inflammatory conditions such as rheumatoid arthritis or sepsis, the regulatory mechanisms of inflammation are inefficient and the excessive inflammatory response leads to damage to the host. Sirtuins are class III histone deacetylases that modulate the activity of several transcription factors that are implicated in immune responses. In this study, we evaluated the impact of sirtuin inhibition on the activation of lipopolysaccharide (LPS)-stimulated J774 macrophages by assessing the production of inflammatory cytokines. The pharmacologic inhibition of sirtuins decreased the production of tumour necrosis factor-alpha (TNF-alpha) interleukin 6 (IL-6) and Rantes. The reduction of cytokine production was associated with decreased nuclear factor kappa B (NF-kappaB) activity and inhibitor kappa B alpha (IkappaBalpha) phosphorylation while no impact was observed on the phosphorylation status of p38 mitogen-activated kinase (p38 MAPK). This work shows that sirtuin pharmacologic inhibitors are a promising tool for the treatment of inflammatory conditions.

Disciplines :

Biochemistry, biophysics & molecular biology

Author, co-author :

Fernandes, Claudia A.

Fievez, Laurence ; Université de Liège - ULiège > Département de sciences fonctionnelles > GIGA-R : Biochimie et biologie moléculaire

Neyrinck, Audrey M.

Delzenne, Nathalie M.

Bureau, Fabrice ; Université de Liège - ULiège > Département de sciences fonctionnelles > GIGA-R : Biochimie et biologie moléculaire

Vanbever, Rita

Language :

English

Title :

Sirtuin inhibition attenuates the production of inflammatory cytokines in lipopolysaccharide-stimulated macrophages.

Publication date :

2012

Journal title :

Biochemical and Biophysical Research Communications

ISSN :

0006-291X

eISSN :

1090-2104

Publisher :

Elsevier, Atlanta, United States - California

Volume :

420

Issue :

Pages :

857-861

Peer reviewed :

Peer reviewed

Available on ORBi :

since 28 November 2012

Statistics

Number of views

133 (1 by ULiège)

Number of downloads

0 (0 by ULiège)

More statistics

Scopus citations^®

Scopus citations^®
without self-citations

OpenCitations

Bibliography

Bruzzone S., Fruscione F., Morando S., Ferrando T., Poggi A., Garuti A., D'Urso A., Selmo M., Benvenuto F., Cea M., Zoppoli G., Moran E., Soncini D., Ballestrero A., Sordat B., Patrone F., Mostoslavsky R., Uccelli A., Nencioni A. Catastrophic NAD+ depletion in activated T lymphocytes through Nampt inhibition reduces demyelination and disability in EAE. PLoS One 2009, 4:e7897.
Bureau F., Vanderplasschen A., Jaspar F., Minner F., Pastoret P.P., Merville M.P., Bours V., Lekeux P. Constitutive nuclear factor-kappaB activity preserves homeostasis of quiescent mature lymphocytes and granulocytes by controlling the expression of distinct Bcl-2 family proteins. Blood 2002, 99:3683-3691.
Chen L.F., Greene W.C. Shaping the nuclear action of NF-kappaB. Nat. Rev. Mol. Cell Biol. 2004, 5:392-401.
Drexler S.K., Kong P.L., Wales J., Foxwell B.M. Cell signalling in macrophages, the principal innate immune effector cells of rheumatoid arthritis. Arthritis Res. Ther. 2008, 10:216.
Frescas D., Valenti L., Accili D. Nuclear trapping of the forkhead transcription factor FoxO1 via Sirt-dependent deacetylation promotes expression of glucogenetic genes. J. Biol. Chem. 2005, 280:20589-20595.
Gao Z., Ye J. Inhibition of transcriptional activity of c-JUN by SIRT1. Biochem. Biophys. Res. Commun. 2008, 376:793-796.
Gordon S. The macrophage: past, present and future. Eur. J. Immunol. 2007, 37(Suppl. 1):S9-S17.
Heltweg B., Gatbonton T., Schuler A.D., Posakony J., Li H., Goehle S., Kollipara R., Depinho R.A., Gu Y., Simon J.A., Bedalov A. Antitumor activity of a small-molecule inhibitor of human silent information regulator 2 enzymes. Cancer Res. 2006, 66:4368-4377.
Heltweg B., Jung M. A microplate reader-based nonisotopic histone deacetylase activity assay. Anal. Biochem. 2002, 302:175-183.
Jung-Hynes B., Ahmad N. Role of p53 in the anti-proliferative effects of Sirt1 inhibition in prostate cancer cells. Cell Cycle 2009, 8:1478-1483.
Kawahara T.L., Michishita E., Adler A.S., Damian M., Berber E., Lin M., McCord R.A., Ongaigui K.C., Boxer L.D., Chang H.Y., Chua K.F. SIRT6 links histone H3 lysine 9 deacetylation to NF-kappaB-dependent gene expression and organismal life span. Cell 2009, 136:62-74.
Kotlyarov A., Neininger A., Schubert C., Eckert R., Birchmeier C., Volk H.D., Gaestel M. MAPKAP kinase 2 is essential for LPS-induced TNF-alpha biosynthesis. Nat. Cell Biol. 1999, 1:94-97.
Legutko A., Marichal T., Fievez L., Bedoret D., Mayer A., de V.H., Klotz L., Drion P.V., Heirman C., Cataldo D., Louis R., Thielemans K., Andris F., Leo O., Lekeux P., Desmet C.J., Bureau F. Sirtuin 1 promotes Th2 responses and airway allergy by repressing peroxisome proliferator-activated receptor-{gamma} activity in dendritic cells. J. Immunol. 2011, 187:4517-4529.
North B.J., Marshall B.L., Borra M.T., Denu J.M., Verdin E. The human Sir2 ortholog, SIRT2, is an NAD+-dependent tubulin deacetylase. Mol. Cell 2003, 11:437-444.
Palsson-McDermott E.M., O'Neill L.A. Signal transduction by the lipopolysaccharide receptor, Toll-like receptor-4. Immunology 2004, 113:153-162.
Rajendrasozhan S., Yang S.R., Kinnula V.L., Rahman I. SIRT1, an antiinflammatory and antiaging protein, is decreased in lungs of patients with chronic obstructive pulmonary disease. Am. J. Respir. Crit. Care Med. 2008, 177:861-870.
Saccani S., Pantano S., Natoli G. P38-Dependent marking of inflammatory genes for increased NF-kappa B recruitment. Nat. Immunol. 2002, 3:69-75.
Schug T.T., Xu Q., Gao H., Peres-da-Silva A., Draper D.W., Fessler M.B., Purushotham A., Li X. Myeloid deletion of SIRT1 induces inflammatory signaling in response to environmental stress. Mol. Cell Biol. 2010, 30:4712-4721.
Shen Z., Ajmo J.M., Rogers C.Q., Liang X., Le L., Murr M.M., Peng Y., You M. Role of SIRT1 in regulation of LPS- or two ethanol metabolites-induced TNF-alpha production in cultured macrophage cell lines. Am. J. Physiol. Gastrointest. Liver Physiol. 2009, 296:G1047-G1053.
Smith J.W., Gamelli R.L., Jones S.B., Shankar R. Immunologic responses to critical injury and sepsis. J. Intensive Care Med. 2006, 21:160-172.
Symons A., Beinke S., Ley S.C. MAP kinase kinase kinases and innate immunity. Trends Immunol. 2006, 27:40-48.
Takeuchi O., Akira S. Pattern recognition receptors and inflammation. Cell 2010, 140:805-820.
Taylor D.M., Maxwell M.M., Luthi-Carter R., Kazantsev A.G. Biological and potential therapeutic roles of sirtuin deacetylases. Cell Mol. Life Sci. 2008, 65:4000-4018.
Van Gool F., Galli M., Gueydan C., Kruys V., Prevot P.P., Bedalov A., Mostoslavsky R., Alt F.W., De S.T., Leo O. Intracellular NAD levels regulate tumor necrosis factor protein synthesis in a sirtuin-dependent manner. Nat. Med. 2009, 15:206-210.
Vroman B., Mazza M., Fernandez M.R., Jerome R., Preat V. Copolymers of epsilon-caprolactone and quaternized epsilon-caprolactone as gene carriers. J. Control Release 2007, 118:136-144.
Yeung F., Hoberg J.E., Ramsey C.S., Keller M.D., Jones D.R., Frye R.A., Mayo M.W. Modulation of NF-kappaB-dependent transcription and cell survival by the SIRT1 deacetylase. EMBO J. 2004, 23:2369-2380.