Abstract
Histone deacetylases (HDACs) are a family of 18 members that participate in the epigenetic regulation of gene expression. In addition to histones, some HDACs also deacetylate transcription factors and specific cytoplasmic proteins.
Monocytes, as part of the innate immune system, maintain tissue homeostasis and help fight infections and cancer. In these cells, HDACs are involved in multiple processes including proliferation, migration, differentiation, inflammatory response, infections, and tumorigenesis. Here, a systematic description of the role that most HDACs play in these functions is reviewed. Specifically, some HDACs induce a pro-inflammatory response and play major roles in host defense. Conversely, other HDACs reprogram monocytes and macrophages towards an immunosuppressive phenotype. The right balance between both types helps monocytes to respond correctly to the different physiological/pathological stimuli. However, aberrant expressions or activities of specific HDACs are associated with autoimmune diseases along with other chronic inflammatory diseases, infections, or cancer.
This paper critically reviews the interesting and extensive knowledge regarding the role of some HDACs in these pathologies. It also shows that as yet, very little progress has been made toward the goal of finding effective HDAC-targeted therapies. However, given their obvious potential, we conclude that it is worth the effort to develop monocyte-specific drugs that selectively target HDAC subtypes with the aim of finding effective treatments for diseases in which our innate immune system is involved.
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Abbreviations
- BMDMs:
-
Bone marrow–derived macrophage cells
- COPD:
-
Chronic obstructive pulmonary disease
- COX-2:
-
Cyclooxygenase 2
- CSE:
-
Cigarette smoke extract
- FDA:
-
Food and Drug Administration
- FOXO:
-
Forkhead box
- HAT:
-
Histone acetyltransferase
- HDAC:
-
Histone deacetylase
- HIF-1α:
-
Hypoxia-inducible factor 1 alpha
- HIV-1:
-
Human immunodeficiency virus 1
- HSPCs:
-
Human stem and progenitor cells
- IAV:
-
Influenza A virus
- IL:
-
Interleukin
- JEV:
-
Japanese encephalitis virus
- KLF2:
-
Krüppel-like factor 2
- LOX-1:
-
Lectin-like oxidized low-density lipoprotein receptor-1
- LPMCs:
-
Intestinal lamina propia mononuclear cells
- LPS:
-
Lipopolysaccharide
- LXR:
-
Liver X receptor
- MCP-1:
-
Monocyte chemoattractant protein
- MEF2:
-
Myocyte enhancer factor 2
- MIP-1α:
-
Macrophage inflammatory protein alpha
- MMP9:
-
Matrix metalloproteinase-9
- NES:
-
Nuclear export sequence
- NF-ĸB:
-
Nuclear factor kappa B
- NLS:
-
Nuclear localization sequence
- Nrf2:
-
Nuclear factor erythroid 2-related factor 2
- PBMCs:
-
Peripheral blood mononuclear cells
- PI3Kδ:
-
Phosphoinositide-3-kinase-δ
- SAHA:
-
Suberoylanilide hydroxamic acid
- SIRT:
-
Sirtuin
- TLR:
-
Toll-like receptor
- TNFα:
-
Tumoral necrosis factor alpha
References
Adenuga D, Yao H, March TH et al (2009) Histone deacetylase 2 is phosphorylated, ubiquitinated, and degraded by cigarette smoke. Am J Respir Cell Mol Biol 40:464–473. https://doi.org/10.1165/rcmb.2008-0255OC
Adhya D, Dutta K, Kundu K, Basu A (2013) Histone deacetylase inhibition by Japanese encephalitis virus in monocyte/macrophages: a novel viral immune evasion strategy. Immunobiology 218:1235–1247. https://doi.org/10.1016/j.imbio.2013.04.018
Algate K, Haynes D, Fitzsimmons T et al (2020) Histone deacetylases 1 and 2 inhibition suppresses cytokine production and osteoclast bone resorption in vitro. J Cell Biochem 121:244–258. https://doi.org/10.1002/jcb.29137
Angiolilli C, Baeten DL, Radstake TR, Reedquist KA (2017) The acetyl code in rheumatoid arthritis and other rheumatic diseases. Epigenomics 9:447–461
Annamanedi M, Kalle AM (2014) Celecoxib sensitizes Staphylococcus aureus to antibiotics in macrophages by modulating SIRT1. PLoS One 9:e99285. https://doi.org/10.1371/journal.pone.0099285
Aude-Garcia C, Collin-Faure V, Bausinger H et al (2010) Dual roles for MEF2A and MEF2D during human macrophage terminal differentiation and c-Jun expression. Biochem J 430:237–244. https://doi.org/10.1042/BJ20100131
Barnes PJ (2009) Role of HDAC2 in the pathophysiology of COPD. Annu Rev Physiol 71:451–464
Barnes PJ (2010) Theophylline. Pharmaceuticals 3:725–747
Barnes PJ (2013) Development of new drugs for COPD. Curr Med Chem 20:1531–1540. https://doi.org/10.2174/0929867311320120005
Boniakowski AM, den Dekker AD, Davis FM et al (2019) SIRT3 regulates macrophage-mediated inflammation in diabetic wound repair. J Invest Dermatol 139:2528–2537.e2. https://doi.org/10.1016/j.jid.2019.05.017
Breitenstein A, Wyss CA, Spescha RD et al (2013) Peripheral blood monocyte Sirt1 expression is reduced in patients with coronary artery disease. PLoS One 8. https://doi.org/10.1371/journal.pone.0053106
Cantley MD, Fairlie DP, Bartold PM et al (2011) Inhibitors of histone deacetylases in class I and class II suppress human osteoclasts in vitro. J Cell Physiol 226:3233–3241. https://doi.org/10.1002/jcp.22684
Cao J, Sun L, Aramsangtienchai P et al (2019) HDAC11 regulates type I interferon signaling through defatty-acylation of SHMT2. Proc Natl Acad Sci U S A 116:5487–5492. https://doi.org/10.1073/pnas.1815365116
Carta S, Tassi S, Semino C et al (2006) Histone deacetylase inhibitors prevent exocytosis of interleukin-1β- containing secretory lysosomes: role of microtubules. Blood 108:1618–1626. https://doi.org/10.1182/blood-2006-03-014126
Castellucci M, Rossato M, Calzetti F et al (2015) IL-10 disrupts the Brd4-docking sites to inhibit LPS-induced CXCL8 and TNF-α expression in monocytes: implications for chronic obstructive pulmonary disease. J Allergy Clin Immunol 136:781–791.e9. https://doi.org/10.1016/j.jaci.2015.04.023
Chan SH, Hung CH, Shih JY et al (2017) SIRT1 inhibition causes oxidative stress and inflammation in patients with coronary artery disease. Redox Biol 13:301–309. https://doi.org/10.1016/j.redox.2017.05.027
Chang HH, Wang W, Bong SJ et al (2008a) Protein kinase D-dependent phosphorylation and nuclear export of histone deacetylase 5 mediates vascular endothelial growth factor-induced gene expression and angiogenesis. J Biol Chem 283:14590–14599. https://doi.org/10.1074/jbc.M800264200
Chang YH, Lin IL, Tsay GJ et al (2008b) Elevated circulatory MMP-2 and MMP-9 levels and activities in patients with rheumatoid arthritis and systemic lupus erythematosus. Clin Biochem 41:955–959. https://doi.org/10.1016/j.clinbiochem.2008.04.012
Charron CE, Chou PC, Coutts DJC et al (2009) Hypoxia-inducible factor 1α induces corticosteroid-insensitive inflammation via reduction of histone deacetylase-2 transcription. J Biol Chem 284:36047–36054. https://doi.org/10.1074/jbc.M109.025387
Chen LF, Greene WC (2004) Shaping the nuclear action of NF-κB. Nat Rev Mol Cell Biol 5:392–401
Choo QY, Ho PC, Tanaka Y, Lin HS (2013) The histone deacetylase inhibitors MS-275 and SAHA suppress the p38 mitogen-activated protein kinase signaling pathway and chemotaxis in rheumatoid arthritic synovial fibroblastic E11 cells. Molecules 18:14085–14095. https://doi.org/10.3390/molecules181114085
Collins T, Cybulsky MI (2001) NF-κB: pivotal mediator or innocent bystander in atherogenesis? J Clin Invest 107:255–264
Cosio BG, Tsaprouni L, Ito K et al (2004) Theophylline restores histone deacetylase activity and steroid responses in COPD macrophages. J Exp Med 200:689–695. https://doi.org/10.1084/jem.20040416
Cosío BG, Jahn A, Iglesias A et al (2015) Haemophilus influenzae induces steroid-resistant inflammatory responses in COPD. BMC Pulm Med 15:157. https://doi.org/10.1186/s12890-015-0155-3
Crane MJ, Hokeness-Antonelli KL, Salazar-Mather TP (2009) Regulation of inflammatory monocyte/macrophage recruitment from the bone marrow during murine cytomegalovirus infection: role for type I interferons in localized induction of CCR2 ligands. J Immunol 183:2810–2817. https://doi.org/10.4049/jimmunol.0900205
Crosbie PAJ, Woodhead MA (2009) Long-term macrolide therapy in chronic inflammatory airway diseases. Eur Respir J 33:171–181
Crujeiras AB, Parra D, Goyenechea E, Martínez JA (2008) Sirtuin gene expression in human mononuclear cells is modulated by caloric restriction. Eur J Clin Investig 38:672–678. https://doi.org/10.1111/j.1365-2362.2008.01998.x
Dai Y, Rahmani M, Dent P, Grant S (2005) Blockade of histone deacetylase inhibitor-induced RelA/p65 acetylation and NF-κB activation potentiates apoptosis in leukemia cells through a process mediated by oxidative damage, XIAP downregulation, and c-Jun N-terminal kinase 1 activation. Mol Cell Biol 25:5429–5444. https://doi.org/10.1128/mcb.25.13.5429-5444.2005
Dali-Youcef N, Lagouge M, Froelich S et al (2007) Sirtuins: the “magnificent seven”, function, metabolism and longevity. Ann Med 39:335–345
Das Gupta K, Shakespear MR, Iyer A et al (2016) Histone deacetylases in monocyte/macrophage development, activation and metabolism: refining HDAC targets for inflammatory and infectious diseases. Clin Trans Immunol 5:e62
Daskalaki MG, Tsatsanis C, Kampranis SC (2018) Histone methylation and acetylation in macrophages as a mechanism for regulation of inflammatory responses. J Cell Physiol 233:6495–6507
De Kreutzenberg SV, Ceolotto G, Papparella I et al (2010) Downregulation of the longevity-associated protein sirtuin 1 in insulin resistance and metabolic syndrome: potential biochemical mechanisms. Diabetes 59:1006–1015. https://doi.org/10.2337/db09-1187
De Ruijter AJM, Van Gennip AH, Caron HN et al (2003) Histone deacetylases (HDACs): characterization of the classical HDAC family. Biochem J 370:737–749
Dutot M, Fagon R, Hemon M, Rat P (2012) Antioxidant, anti-inflammatory, and anti-senescence activities of a phlorotannin-rich natural extract from Brown Seaweed Ascophyllum nodosum. Appl Biochem Biotechnol 167:2234–2240. https://doi.org/10.1007/s12010-012-9761-1
Eccleston A, DeWitt N, Gunter C et al (2007) Epigenetics. Nature 447:395
Elmali N, Baysal O, Harma A et al (2007) Effects of resveratrol in inflammatory arthritis. Inflammation 30:1–6. https://doi.org/10.1007/s10753-006-9012-0
Eskandarian HA, Impens F, Nahori M-A et al (2013) A role for SIRT2-dependent histone H3K18 deacetylation in bacterial infection. Science 341:1238858. https://doi.org/10.1126/science.1238858
Ewelina W, Tomasz P, Agnieszka R (2017) Downregulation of PARP1 transcription by promoter-associated E2F4-RBL2-HDAC1-BRM complex contributes to repression of pluripotency stem cell factors in human monocytes. Sci Rep 7:9483. https://doi.org/10.1038/s41598-017-10307-z
Footitt J, Mallia P, Durham AL et al (2016) Oxidative and nitrosative stress and histone deacetylase-2 activity in exacerbations of COPD. Chest 149:62–73. https://doi.org/10.1378/chest.14-2637
Gan L, Li C, Wang J, Guo X (2016) Curcumin modulates the effect of histone modification on the expression of chemokines by type II alveolar epithelial cells in a rat COPD model. Int J COPD 11:2765–2773. https://doi.org/10.2147/COPD.S113978
Ghosh S, Karin M (2002) Missing pieces in the NF-κB puzzle. Cell 109:S81–S96
Guerriero JL, Sotayo A, Ponichtera HE et al (2017) Class IIa HDAC inhibition reduces breast tumours and metastases through anti-tumour macrophages. Nature 543:428–432. https://doi.org/10.1038/nature21409
Guo X, Deng J, Zheng B et al (2020) HDAC1 and HDAC2 regulate anti-inflammatory effects of anesthetic isoflurane in human monocytes. Immunol Cell Biol 98:318–331. https://doi.org/10.1111/imcb.12318
Ha CH, Kim JY, Zhao J et al (2010) PKA phosphorylates histone deacetylase 5 and prevents its nuclear export, leading to the inhibition of gene transcription and cardiomyocyte hypertrophy. Proc Natl Acad Sci U S A 107:15467–15472. https://doi.org/10.1073/pnas.1000462107
Ha SD, Cho W, Kim SO (2017) HDAC8 prevents anthrax lethal toxin-induced cell cycle arrest through silencing PTEN in human monocytic THP-1 cells. Toxins 9:162. https://doi.org/10.3390/toxins9050162
Hackanson B, Rimmele L, Benkißer M et al (2012) HDAC6 as a target for antileukemic drugs in acute myeloid leukemia. Leuk Res 36:1055–1062. https://doi.org/10.1016/j.leukres.2012.02.026
Hah YS, Cheon YH, Lim HS et al (2014) Myeloid deletion of SIRT1 aggravates serum transfer arthritis in mice via nuclear factor-κB activation. PLoS One 9:e87733. https://doi.org/10.1371/journal.pone.0087733
Hashimoto A, Fukumoto T, Zhang R, Gabrilovich D (2020) Selective targeting of different populations of myeloid-derived suppressor cells by histone deacetylase inhibitors. Cancer Immunol Immunother 69:1929–1936. https://doi.org/10.1007/s00262-020-02588-7
Heim CE, Bosch ME, Yamada KJ et al (2020) Lactate production by Staphylococcus aureus biofilm inhibits HDAC11 to reprogramme the host immune response during persistent infection. Nat Microbiol 5:1271–1284. https://doi.org/10.1038/s41564-020-0756-3
Hoeksema MA, Gijbels MJ, Van den Bossche J et al (2014) Targeting macrophage histone deacetylase 3 stabilizes atherosclerotic lesions. EMBO Mol Med 6:1124–1132. https://doi.org/10.15252/emmm.201404170
Hubbert C, Guardiola A, Shao R et al (2002) HDAC6 is a microtubule-associated deacetylase. Nature 417:455–458. https://doi.org/10.1038/417455a
Hui Ng H, Bird A (2000) Histone deacetylases: silencers for hire. Trends Biochem Sci 25:121–126
Ishida T, Yoshida T, Shinohara K et al (2017) Potential role of sirtuin 1 in Müller glial cells in mice choroidal neovascularization. PLoS One 12:e0183775. https://doi.org/10.1371/journal.pone.0183775
Ito K, Lim S, Caramori G et al (2002) A molecular mechanism of action of theophylline: induction of histone deacetylase activity to decrease inflammatory gene expression. Proc Natl Acad Sci U S A 99:8921–8926. https://doi.org/10.1073/pnas.132556899
Ito K, Ito M, Elliott WM et al (2005) Decreased histone deacetylase activity in chronic obstructive pulmonary disease. N Engl J Med 352:1967–1976. https://doi.org/10.1056/NEJMoa041892
Jan JS, Chou YC, Cheng YW et al (2017) The novel HDAC8 inhibitor WK2-16 attenuates lipopolysaccharide-activated matrix metalloproteinase-9 expression in human monocytic cells and improves hypercytokinemia in vivo. Int J Mol Sci 18:1394. https://doi.org/10.3390/ijms18071394
Ji L, Chen Y, Wang H et al (2019) Overexpression of Sirt6 promotes M2 macrophage transformation, alleviating renal injury in diabetic nephropathy. Int J Oncol 55:103–115. https://doi.org/10.3892/ijo.2019.4800
Jin Z, Xiao Y, Yao F et al (2020) SIRT6 inhibits cholesterol crystal-induced vascular endothelial dysfunction via Nrf2 activation. Exp Cell Res 387:111744. https://doi.org/10.1016/j.yexcr.2019.111744
Johnson CA, White DA, Lavender JS et al (2002) Human class I histone deacetylase complexes show enhanced catalytic activity in the presence of ATP and co-immunoprecipitate with the ATP-dependent chaperone protein Hsp70. J Biol Chem 277:9590–9597. https://doi.org/10.1074/jbc.M107942200
Kaiser A, Schmidt M, Huber O et al (2020) SIRT7: an influence factor in healthy aging and the development of age-dependent myeloid stem-cell disorders. Leukemia 34:2206–2216. https://doi.org/10.1038/s41375-020-0803-3
Kauppinen A, Suuronen T, Ojala J et al (2013) Antagonistic crosstalk between NF-κB and SIRT1 in the regulation of inflammation and metabolic disorders. Cell Signal 25:1939–1948
Kawabata T, Nishida K, Takasugi K et al (2010) Increased activity and expression of histone deacetylase 1 in relation to tumor necrosis factor-alpha in synovial tissue of rheumatoid arthritis. Arthritis Res Ther 12:R133. https://doi.org/10.1186/ar3071
Kawahara TLA, Michishita E, Adler AS et al (2009) SIRT6 links histone H3 lysine 9 deacetylation to NF-κB-dependent gene expression and organismal life span. Cell 136:62–74. https://doi.org/10.1016/j.cell.2008.10.052
Kiernan R, Brès V, Ng RWM et al (2003) Post-activation turn-off of NF-κB-dependent transcription is regulated by acetylation of p65. J Biol Chem 278:2758–2766. https://doi.org/10.1074/jbc.M209572200
Kim A, Lee W, Yun JM (2017) Luteolin and fisetin suppress oxidative stress by modulating sirtuins and forkhead box O3a expression under in vitro diabetic conditions. Nutr Res Pract 11:430–434. https://doi.org/10.4162/nrp.2017.11.5.430
Kim TS, Jin YB, Kim YS et al (2019) SIRT3 promotes antimycobacterial defenses by coordinating mitochondrial and autophagic functions. Autophagy 15:1356–1375. https://doi.org/10.1080/15548627.2019.1582743
Kitada M, Ogura Y, Koya D (2016) The protective role of Sirt1 in vascular tissue: its relationship to vascular aging and atherosclerosis. Aging 8:2290–2307
Kobayashi T, Matsuoka K, Sheikh SZ et al (2012) IL-10 regulates Il12b expression via histone deacetylation: implications for intestinal macrophage homeostasis. J Immunol 189:1792–1799. https://doi.org/10.4049/jimmunol.1200042
Kobayashi Y, Wada H, Rossios C et al (2013) A novel macrolide/fluoroketolide, solithromycin (CEM-101), reverses corticosteroid insensitivity via phosphoinositide 3-kinase pathway inhibition. Br J Pharmacol 169:1024–1034. https://doi.org/10.1111/bph.12187
Kumar A, Lin Z, SenBanerjee S, Jain MK (2005) Tumor necrosis factor alpha-mediated reduction of KLF2 is due to inhibition of MEF2 by NF-κB and histone deacetylases. Mol Cell Biol 25:5893–5903. https://doi.org/10.1128/mcb.25.14.5893-5903.2005
Kutil Z, Novakova Z, Meleshin M et al (2018) Histone deacetylase 11 is a fatty-acid deacylase. ACS Chem Biol 13:685–693. https://doi.org/10.1021/acschembio.7b00942
Kwon IS, Wang W, Xu S, Jin ZG (2014) Histone deacetylase 5 interacts with Krüppel-like factor 2 and inhibits its transcriptional activity in endothelium. Cardiovasc Res 104:127–137. https://doi.org/10.1093/cvr/cvu183
Laubach JP, San-Miguel JF, Hungria V et al (2017) Deacetylase inhibitors: an advance in myeloma therapy? Expert Rev Hematol 10:229–237
Lee SM, Yang H, Tartar DM et al (2011) Prevention and treatment of diabetes with resveratrol in a non-obese mouse model of type 1 diabetes. Diabetologia 54:1136–1146. https://doi.org/10.1007/s00125-011-2064-1
Lee HS, Ka SO, Lee SM et al (2013) Overexpression of sirtuin 6 suppresses inflammatory responses and bone destruction in mice with collagen-induced arthritis. Arthritis Rheum 65:1776–1785. https://doi.org/10.1002/art.37963
Lee W, Lee SY, Son YJ, Yun JM (2015) Gallic acid decreases inflammatory cytokine secretion through histone acetyltransferase/histone deacetylase regulation in high glucose-induced human monocytes. J Med Food 18:793–801. https://doi.org/10.1089/jmf.2014.3342
Leus NGJ, Zwinderman MRH, Dekker FJ (2016) Histone deacetylase 3 (HDAC 3) as emerging drug target in NF-κB-mediated inflammation. Curr Opin Chem Biol 33:160–168
Li M, Zhong X, He Z et al (2012) Effect of erythromycin on cigarette-induced histone deacetylase protein expression and nuclear factor-κB activity in human macrophages in vitro. Int Immunopharmacol 12:643–650. https://doi.org/10.1016/j.intimp.2011.12.022
Li S, Fossati G, Marchetti C et al (2015) Specific inhibition of histone deacetylase 8 reduces gene expression and production of proinflammatory cytokines in vitro and in vivo. J Biol Chem 290:2368–2378. https://doi.org/10.1074/jbc.M114.618454
Li Y, Ni J, Guo R, Li W (2016) In patients with coronary artery disease and type 2 diabetes, SIRT1 expression in circulating mononuclear cells is associated with levels of inflammatory cytokines but not with coronary lesions. Biomed Res Int 2016:8734827. https://doi.org/10.1155/2016/8734827
Li X, Zhang Y, Jiang Y et al (2017a) Selective HDAC inhibitors with potent oral activity against leukemia and colorectal cancer: design, structure-activity relationship and anti-tumor activity study. Eur J Med Chem 134:185–206. https://doi.org/10.1016/j.ejmech.2017.03.069
Li Z, Bridges B, Olson J, Weinman SA (2017b) The interaction between acetylation and serine-574 phosphorylation regulates the apoptotic function of FOXO3. Oncogene 36:1887–1898. https://doi.org/10.1038/onc.2016.359
Liao W, Tan WSD, Wong WSF (2016) Andrographolide restores steroid sensitivity to block lipopolysaccharide/IFN-γ–induced IL-27 and airway hyperresponsiveness in mice. J Immunol 196:4706–4712. https://doi.org/10.4049/jimmunol.1502114
Liu TF, Yoza BK, El Gazzar M et al (2011) NAD+-dependent SIRT1 deacetylase participates in epigenetic reprogramming during endotoxin tolerance. J Biol Chem 286:9856–9864. https://doi.org/10.1074/jbc.M110.196790
Liu TF, Vachharajani V, Millet P et al (2015) Sequential actions of SIRT1-RELB-SIRT3 coordinate nuclear-mitochondrial communication during immunometabolic adaptation to acute inflammation and sepsis. J Biol Chem 290:396–408. https://doi.org/10.1074/jbc.M114.566349
Liu Z, Wang J, Huang X et al (2016) Deletion of sirtuin 6 accelerates endothelial dysfunction and atherosclerosis in apolipoprotein E-deficient mice. Transl Res 172:18–29.e2. https://doi.org/10.1016/j.trsl.2016.02.005
Liu SS, Wu F, Jin YM et al (2020) HDAC11: a rising star in epigenetics. Biomed Pharmacother 131:110607
Lombard DB, Miller RA (2012) Ageing: sorting out the sirtuins. Nature 483:166–167
Long J, Jia MY, Fang WY et al (2020) FLT3 inhibition upregulates HDAC8 via FOXO to inactivate p53 and promote maintenance of FLT3-ITD1 acute myeloid leukemia. Blood 135:1472–1483. https://doi.org/10.1182/BLOOD.2019003538
Lv L, Wang Q, Xu Y et al (2018) Vpr targets TET2 for degradation by CRL4 VprBP E3 ligase to sustain IL-6 expression and enhance HIV-1 replication. Mol Cell 70:961–970.e5. https://doi.org/10.1016/j.molcel.2018.05.007
Mariani S, Fiore D, Basciani S et al (2015) Plasma levels of SIRT1 associate with non-alcoholic fatty liver disease in obese patients. Endocrine 49:711–716. https://doi.org/10.1007/s12020-014-0465-x
Marwick JA, Adcock IM, Chung KF (2010) Overcoming reduced glucocorticoid sensitivity in airway disease: molecular mechanisms and therapeutic approaches. Drugs 70:929–948
Matalon S, Palmer BE, Nold MF et al (2010) The histone deacetylase inhibitor ITF2357 decreases surface CXCR4 and CCR5 expression on CD4+ T-cells and monocytes and is superior to valproic acid for latent HIV-1 expression in vitro. J Acquir Immune Defic Syndr 54:1–9. https://doi.org/10.1097/QAI.0b013e3181d3dca3
Mathias RA, Guise AJ, Cristea IM (2015) Post-translational modifications regulate class IIa histone deacetylase (HDAC) function in health and disease. Mol Cell Proteomics 14:456–470
Mayo MW, Denlinger CE, Broad RM et al (2003) Ineffectiveness of histone deacetylase inhibitors to induce apoptosis involves the transcriptional activation of NF-κB through the Akt pathway. J Biol Chem 278:18980–18989. https://doi.org/10.1074/jbc.M211695200
McKinsey TA, Zhang CL, Olson EN (2001) Identification of a signal-responsive nuclear export sequence in class II histone deacetylases. Mol Cell Biol 21:6312–6321. https://doi.org/10.1128/mcb.21.18.6312-6321.2001
Meja KK, Rajendrasozhan S, Adenuga D et al (2008) Curcumin restores corticosteroid function in monocytes exposed to oxidants by maintaining HDAC2. Am J Respir Cell Mol Biol 39:312–323. https://doi.org/10.1165/rcmb.2008-0012OC
Mercado N, Thimmulappa R, Thomas CMR et al (2011a) Decreased histone deacetylase 2 impairs Nrf2 activation by oxidative stress. Biochem Biophys Res Commun 406:292–298. https://doi.org/10.1016/j.bbrc.2011.02.035
Mercado N, To Y, Ito K, Barnes PJ (2011b) Nortriptyline reverses corticosteroid insensitivity by inhibition of phosphoinositide-3-kinase-δ. J Pharmacol Exp Ther 337:465–470. https://doi.org/10.1124/jpet.110.175950
Moore KJ, Sheedy FJ, Fisher EA (2013) Macrophages in atherosclerosis: a dynamic balance. Nat Rev Immunol 13:709–721
Moschen AR, Wieser V, Gerner RR et al (2013) Adipose tissue and liver expression of SIRT1, 3, and 6 increase after extensive weight loss in morbid obesity. J Hepatol 59:1315–1322. https://doi.org/10.1016/j.jhep.2013.07.027
Motta MC, Divecha N, Lemieux M et al (2004) Mammalian SIRT1 represses forkhead transcription factors. Cell 116:551–563. https://doi.org/10.1016/S0092-8674(04)00126-6
Moussa C, Hebron M, Huang X et al (2017) Resveratrol regulates neuro-inflammation and induces adaptive immunity in Alzheimer’s disease. J Neuroinflammation 14:1. https://doi.org/10.1186/s12974-016-0779-0
Mullican SE, Gaddis CA, Alenghat T et al (2011) Histone deacetylase 3 is an epigenomic brake in macrophage alternative activation. Genes Dev 25:2480–2488. https://doi.org/10.1101/gad.175950.111
Nagesh PT, Hussain M, Galvin HD, Husain M (2017) Histone deacetylase 2 is a component of influenza A virus-induced host antiviral response. Front Microbiol 8:1315. https://doi.org/10.3389/fmicb.2017.01315
Nakamaru Y, Vuppusetty C, Wada H et al (2009) A protein deacetylase SIRT1 is a negative regulator of metalloproteinase-9. FASEB J 23:2810–2819. https://doi.org/10.1096/fj.08-125468
Narita T, Weinert BT, Choudhary C (2019) Functions and mechanisms of non-histone protein acetylation. Nat Rev Mol Cell Biol 20:156–174
Neele AE, Van Den Bossche J, Hoeksema MA, De Winther MPJ (2015) Epigenetic pathways in macrophages emerge as novel targets in atherosclerosis. Eur J Pharmacol 763:79–89. https://doi.org/10.1016/j.ejphar.2015.03.101
Neurath MF, Fuss I, Schürmann G et al (1998) Cytokine gene transcription by NF-κB family members in patients with inflammatory bowel disease. In: Annals of the New York Academy of Sciences. New York Academy of Sciences, pp 149–159
Nicholas D, Tang H, Zhang Q et al (2015) Quantitative proteomics reveals a role for epigenetic reprogramming during human monocyte differentiation. Mol Cell Proteomics 14:15–29. https://doi.org/10.1074/mcp.M113.035089
Osoata GO, Yamamura S, Ito M et al (2009) Nitration of distinct tyrosine residues causes inactivation of histone deacetylase 2. Biochem Biophys Res Commun 384:366–371. https://doi.org/10.1016/j.bbrc.2009.04.128
Ota H, Akishita M, Eto M et al (2007) Sirt1 modulates premature senescence-like phenotype in human endothelial cells. J Mol Cell Cardiol 43:571–579. https://doi.org/10.1016/j.yjmcc.2007.08.008
Paik S, Kim JK, Chung C, Jo EK (2019) Autophagy: a new strategy for host-directed therapy of tuberculosis. Virulence 10:448–459
Park SY, Lee SW, Kim HY et al (2016) SIRT1 inhibits differentiation of monocytes to macrophages: amelioration of synovial inflammation in rheumatoid arthritis. J Mol Med 94:921–931. https://doi.org/10.1007/s00109-016-1402-7
Paroni G, Cernotta N, Russo CD et al (2008) PP2A regulates HDAC4 nuclear import. Mol Biol Cell 19:655–667. https://doi.org/10.1091/mbc.E07-06-0623
Poralla L, Stroh T, Erben U et al (2015) Histone deacetylase 5 regulates the inflammatory response of macrophages. J Cell Mol Med 19:2162–2171. https://doi.org/10.1111/jcmm.12595
Qi J, Singh S, Hua WK et al (2015) HDAC8 inhibition specifically targets Inv(16) acute myeloid leukemic stem cells by restoring p53 acetylation. Cell Stem Cell 17:597–610. https://doi.org/10.1016/j.stem.2015.08.004
Qin K, Han C, Zhang H, et al (2017) NAD+ dependent deacetylase Sirtuin 5 rescues the innate inflammatory response of endotoxin tolerant macrophages by promoting acetylation of p65. J Autoimmun 81:120–129. https://doi.org/10.1016/j.jaut.2017.04.006
Qin Y, Cao L, Hu L (2019) Sirtuin 6 mitigated LPS-induced human umbilical vein endothelial cells inflammatory responses through modulating nuclear factor erythroid 2-related factor 2. J Cell Biochem 120:11305–11317. https://doi.org/10.1002/jcb.28407
Rajendrasozhan S, Yang SR, Kinnula VL, Rahman I (2008) SIRT1, an antiinflammatory and antiaging protein, is decreased in lungs of patients with chronic obstructive pulmonary disease. Am J Respir Crit Care Med 177:861–870. https://doi.org/10.1164/rccm.200708-1269OC
Randall MJ, Haenen GRMM, Bouwman FG et al (2016) The tobacco smoke component acrolein induces glucocorticoid resistant gene expression via inhibition of histone deacetylase. Toxicol Lett 240:43–49. https://doi.org/10.1016/j.toxlet.2015.10.009
Russell REK, Culpitt SV, DeMatos C et al (2002) Release and activity of matrix metalloproteinase-9 and tissue inhibitor of metalloproteinase-1 by alveolar macrophages from patients with chronic obstructive pulmonary disease. Am J Respir Cell Mol Biol 26:602–609. https://doi.org/10.1165/ajrcmb.26.5.4685
Salminen A, Kauppinen A, Suuronen T, Kaarniranta K (2008) SIRT1 longevity factor suppresses NF-κB-driven immune responses: regulation of aging via NF-κB acetylation? BioEssays 30:939–942. https://doi.org/10.1002/bies.20799
Schmeck B, Lorenz J, N’Guessan PD et al (2008) Histone acetylation and flagellin are essential for Legionella pneumophila-induced cytokine expression. J Immunol 181:940–947. https://doi.org/10.4049/jimmunol.181.2.940
Schötterl S, Brennenstuhl H, Naumann U (2015) Modulation of immune responses by histone deacetylase inhibitors. Crit Rev Oncog 20:139–154. https://doi.org/10.1615/CritRevOncog.2014012393
Seidel C, Schnekenburger M, Dicato M, Diederich M (2014) Antiproliferative and proapoptotic activities of 4-hydroxybenzoic acid-based inhibitors of histone deacetylases. Cancer Lett 343:134–146. https://doi.org/10.1016/j.canlet.2013.09.026
Sica A, Erreni M, Allavena P, Porta C (2015) Macrophage polarization in pathology. Cell Mol Life Sci 72:4111–4126
Son SI, Su D, Ho TT, Lin H (2020) Garcinol is an HDAC11 inhibitor. ACS Chem Biol 15:2866–2871. https://doi.org/10.1021/acschembio.0c00719
Song R, Xu W, Chen Y et al (2011) The expression of Sirtuins 1 and 4 in peripheral blood leukocytes from patients with type 2 diabetes. Eur J Histochem 55:e10. https://doi.org/10.4081/ejh.2011.e10
Song MY, Wang J, Ka SO et al (2016) Insulin secretion impairment in Sirt6 knockout pancreatic β cells is mediated by suppression of the FoxO1-Pdx1-Glut2 pathway. Sci Rep 6:30321. https://doi.org/10.1038/srep30321
Stein S, Matter CM (2011) Protective roles of SIRT1 in atherosclerosis. Cell Cycle 10:640–647
Stein S, Lohmann C, Schäfer N et al (2010) SIRT1 decreases Lox-1-mediated foam cell formation in atherogenesis. Eur Heart J 31:2301–2309. https://doi.org/10.1093/eurheartj/ehq107
Sun XJ, Li ZH, Zhang Y et al (2015) Combination of erythromycin and dexamethasone improves corticosteroid sensitivity induced by CSE through inhibiting PI3K-δ/Akt pathway and increasing GR expression. Am J Physiol Lung Cell Mol Physiol 309:L139–L146. https://doi.org/10.1152/ajplung.00292.2014
Sun L, Telles E, Karl M et al (2018) Loss of HDAC11 ameliorates clinical symptoms in a multiple sclerosis mouse model. Life Sci Alliance 1:e201800039. https://doi.org/10.26508/lsa.201800039
Sun R, Hedl M, Abraham C (2019) Twist1 and Twist2 induce human macrophage memory upon chronic innate receptor treatment by HDAC-mediated deacetylation of cytokine promoters. J Immunol 202:3297–3308. https://doi.org/10.4049/jimmunol.1800757
Tabas I, Bornfeldt KE (2016) Macrophage phenotype and function in different stages of atherosclerosis. Circ Res 118:653–667. https://doi.org/10.1161/CIRCRESAHA.115.306256
Tak PP, Firestein GS (2001) NF-κB: a key role in inflammatory diseases. J Clin Invest 107:7–11
Tak Leung Y, Shi L, Maurer K et al (2015) Interferon regulatory factor 1 and histone H4 acetylation in systemic lupus erythematosus. Epigenetics 10:191–199. https://doi.org/10.1080/15592294.2015.1009764
Takeda-Watanabe A, Kitada M, Kanasaki K, Koya D (2012) SIRT1 inactivation induces inflammation through the dysregulation of autophagy in human THP-1 cells. Biochem Biophys Res Commun 427:191–196. https://doi.org/10.1016/j.bbrc.2012.09.042
Takizawa H, Desaki M, Ohtoshi T et al (1995) Erythromycin suppresses interleukin 6 expression by human bronchial epithelial cells: a potential mechanism of its anti-inflammatory action. Biochem Biophys Res Commun 210:781–786. https://doi.org/10.1006/bbrc.1995.1727
Tan C, Xuan L, Cao S et al (2016) Decreased histone deacetylase 2 (HDAC2) in peripheral blood monocytes (PBMCs) of COPD patients. PLoS One 11:e0147380. https://doi.org/10.1371/journal.pone.0147380
Taniguchi M, Carreira MB, Smith LN et al (2012) Histone deacetylase 5 limits cocaine reward through cAMP-induced nuclear import. Neuron 73:108–120. https://doi.org/10.1016/j.neuron.2011.10.032
Tao J, Zhang J, Ling Y et al (2018) Mitochondrial sirtuin 4 resolves immune tolerance in monocytes by rebalancing glycolysis and glucose oxidation homeostasis. Front Immunol 9:9. https://doi.org/10.3389/fimmu.2018.00419
Tarumoto Y, Lu B, Somerville TDD et al (2018) LKB1, salt-inducible kinases, and MEF2C are linked dependencies in acute myeloid leukemia. Mol Cell 69:1017–1027.e6. https://doi.org/10.1016/j.molcel.2018.02.011
Thiagalingam S, Cheng KH, Lee HJ et al (2003) Histone deacetylases: unique players in shaping the epigenetic histone code. In: Annals of the New York Academy of Sciences. New York Academy of Sciences, pp 84–100
To Y, Ito K, Kizawa Y et al (2010) Targeting phosphoinositide-3-kinase-δ with theophylline reverses corticosteroid insensitivity in chronic obstructive pulmonary disease. Am J Respir Crit Care Med 182:897–904. https://doi.org/10.1164/rccm.200906-0937OC
Tu Y, Hershman DL, Bhalla K et al (2014) A phase I-II study of the histone deacetylase inhibitor vorinostat plus sequential weekly paclitaxel and doxorubicin-cyclophosphamide in locally advanced breast cancer. Breast Cancer Res Treat 146:145–152. https://doi.org/10.1007/s10549-014-3008-5
Valente S, Tardugno M, Conte M et al (2011) Novel cinnamyl hydroxyamides and 2-aminoanilides as histone deacetylase inhibitors: apoptotic induction and cytodifferentiation activity. ChemMedChem 6:698–712. https://doi.org/10.1002/cmdc.201000535
Valente S, Trisciuoglio D, Tardugno M et al (2013) Tert-butylcarbamate-containing histone deacetylase inhibitors: apoptosis induction, cytodifferentiation, and antiproliferative activities in cancer cells. ChemMedChem 8:800–811. https://doi.org/10.1002/cmdc.201300005
Van Den Bossche J, Neele AE, Hoeksema MA et al (2014) Inhibiting epigenetic enzymes to improve atherogenic macrophage functions. Biochem Biophys Res Commun 455:396–402. https://doi.org/10.1016/j.bbrc.2014.11.029
Van Kempen LCL, Coussens LM (2002) MMP9 potentiates pulmonary metastasis formation. Cancer Cell 2:251–252
Vaziri H, Dessain SK, Eaton EN et al (2001) hSIR2SIRT1 functions as an NAD-dependent p53 deacetylase. Cell 107:149–159. https://doi.org/10.1016/S0092-8674(01)00527-X
Wang W, Ha CH, Jhun BS et al (2010) Fluid shear stress stimulates phosphorylation-dependent nuclear export of HDAC5 and mediates expression of KLF2 and eNOS. Blood 115:2971–2979. https://doi.org/10.1182/blood-2009-05-224824
Wang Y, Smith W, Hao D et al (2019) M1 and M2 macrophage polarization and potentially therapeutic naturally occurring compounds. Int Immunopharmacol 70:459–466
Watters SA, Mlcochova P, Gupta RK (2013) Macrophages: the neglected barrier to eradication. Curr Opin Infect Dis 26:561–566
West MA, Heagy W (2002) Endotoxin tolerance: a review. Crit Care Med 30:S64–S73
Winkler AR, Nocka KN, Williams CMM (2012) Smoke exposure of human macrophages reduces HDAC3 activity, resulting in enhanced inflammatory cytokine production. Pulm Pharmacol Ther 25:286–292. https://doi.org/10.1016/j.pupt.2012.05.003
Winnik S, Stein S, Matter C (2012) SIRT1 – an anti-inflammatory pathway at the crossroads between metabolic disease and atherosclerosis. Curr Vasc Pharmacol 10:693–696. https://doi.org/10.2174/157016112803520756
Woo SJ, Noh HS, Lee NY et al (2018) Myeloid sirtuin 6 deficiency accelerates experimental rheumatoid arthritis by enhancing macrophage activation and infiltration into synovium. EBioMedicine 38:228–237. https://doi.org/10.1016/j.ebiom.2018.11.005
Xi J, Chen Y, Jing J et al (2019) Sirtuin 3 suppresses the formation of renal calcium oxalate crystals through promoting M2 polarization of macrophages. J Cell Physiol 234:11463–11473. https://doi.org/10.1002/jcp.27803
Xu S, Yin M, Koroleva M et al (2016) SIRT6 protects against endothelial dysfunction and atherosclerosis in mice. Aging 8:1064–1082. https://doi.org/10.18632/aging.100975
Yanagisawa S, Baker JR, Vuppusetty C et al (2018) The dynamic shuttling of SIRT1 between cytoplasm and nuclei in bronchial epithelial cells by single and repeated cigarette smoke exposure. PLoS One 13:e0193921. https://doi.org/10.1371/journal.pone.0193921
Yang WM, Tsai SC, Der Wen Y et al (2002) Functional domains of histone deacetylase-3. J Biol Chem 277:9447–9454. https://doi.org/10.1074/jbc.M105993200
Yang SR, Wright J, Bauter M et al (2007) Sirtuin regulates cigarette smoke-induced proinflammatory mediator release via RelA/p65 NF-κB in macrophages in vitro and in rat lungs in vivo: implications for chronic inflammation and aging. Am J Physiol Lung Cell Mol Physiol 292:L567–L576. https://doi.org/10.1152/ajplung.00308.2006
Yeung F, Hoberg JE, Ramsey CS et al (2004) Modulation of NF-κB-dependent transcription and cell survival by the SIRT1 deacetylase. EMBO J 23:2369–2380. https://doi.org/10.1038/sj.emboj.7600244
Youn GS, Lee KW, Choi SY, Park J (2016) Overexpression of HDAC6 induces pro-inflammatory responses by regulating ROS-MAPK-NF-κB/AP-1 signaling pathways in macrophages. Free Radic Biol Med 97:14–23. https://doi.org/10.1016/j.freeradbiomed.2016.05.014
Zhang R, Chen HZ, Liu JJ et al (2010) SIRT1 suppresses activator protein-1 transcriptional activity and cyclooxygenase-2 expression in macrophages. J Biol Chem 285:7097–7110. https://doi.org/10.1074/jbc.M109.038604
Zhang J, Lazarenko OP, Blackburn ML et al (2013) Blueberry consumption prevents loss of collagen in bone matrix and inhibits senescence pathways in osteoblastic cells. Age 35:807–820. https://doi.org/10.1007/s11357-012-9412-z
Zhang T, Cooper S, Brockdorff N (2015) The interplay of histone modifications – writers that read. EMBO Rep 16:1467–1481. https://doi.org/10.15252/embr.201540945
Zhao S, Zhang X, Li H (2018) Beyond histone acetylation – writing and erasing histone acylations. Curr Opin Struct Biol 53:169–177
Zhao Y, Ma G, Yang X (2019) HDAC5 promotes Mycoplasma pneumoniae-induced inflammation in macrophages through NF-κB activation. Life Sci 221:13–19. https://doi.org/10.1016/j.lfs.2019.02.004
Zhong L, D’Urso A, Toiber D et al (2010) The histone deacetylase Sirt6 regulates glucose homeostasis via Hif1α. Cell 140:280–293. https://doi.org/10.1016/j.cell.2009.12.041
Zhu J, Coyne CB, Sarkar SN (2011) PKC alpha regulates Sendai virus-mediated interferon induction through HDAC6 and β 2-catenin. EMBO J 30:4838–4849. https://doi.org/10.1038/emboj.2011.351
Acknowledgements
We would like to thank the Departamento de Salud (Gobierno de Navarra, Spain) for funding a project focused on the role of different HDACs on peripheral monocytes in depressed patients. Thanks to Ministerio de Ciencia, Innovación y Universidades (Gobierno de España) for supporting to M.C.E (FPU17/05039) with a fellowship. In addition, thanks to all the patients and volunteers that are collaborating in our research, and specially, to Ms Sandra Lizaso for all her technical support in all the monocyte studies. The authors declare no competing interests. Thanks to O.L.F for inspiring me the initial idea of this review during the first weeks of the Covid-19 pandemic.
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Tordera, R.M., Cortés-Erice, M. (2021). Role of Histone Deacetylases in Monocyte Function in Health and Chronic Inflammatory Diseases. In: Pedersen, S.H.F. (eds) Reviews of Physiology, Biochemistry and Pharmacology. Reviews of Physiology, Biochemistry and Pharmacology, vol 180. Springer, Cham. https://doi.org/10.1007/112_2021_59
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