Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.
ADVANCED SEARCH
Log in
Top
Journal of Inflammation
Published in: Journal of Inflammation 1/2011

Open Access 01-12-2011 | Research

Differential patterns of histone acetylation in inflammatory bowel diseases

Authors: Loukia G Tsaprouni, Kazuhiro Ito, Jonathan J Powell, Ian M Adcock, Neville Punchard

Published in: Journal of Inflammation | Issue 1/2011

Login to get access

Abstract

Post-translational modifications of histones, particularly acetylation, are associated with the regulation of inflammatory gene expression. We used two animal models of inflammation of the bowel and biopsy samples from patients with Crohn's disease (CD) to study the expression of acetylated histones (H) 3 and 4 in inflamed mucosa. Acetylation of histone H4 was significantly elevated in the inflamed mucosa in the trinitrobenzene sulfonic acid model of colitis particularly on lysine residues (K) 8 and 12 in contrast to non-inflamed tissue. In addition, acetylated H4 was localised to inflamed tissue and to Peyer's patches (PP) in dextran sulfate sodium (DSS)-treated rat models. Within the PP, H3 acetylation was detected in the mantle zone whereas H4 acetylation was seen in both the periphery and the germinal centre. Finally, acetylation of H4 was significantly upregulated in inflamed biopsies and PP from patients with CD. Enhanced acetylation of H4K5 and K16 was seen in the PP. These results demonstrate that histone acetylation is associated with inflammation and may provide a novel therapeutic target for mucosal inflammation.
Appendix
Available only for authorised users
Literature
1.
Baumgart DC, Carding SR: Inflammatory bowel disease: cause and immunobiology. Lancet. 2007, 369 (9573): 1627-1640. 10.1016/S0140-6736(07)60750-8.PubMedCrossRef
2.
D'Haens G, Daperno M: Advances in biologic therapy for ulcerative colitis and Crohn's disease. Curr Gastroenterol. 2006, 8 (6): 506-512.CrossRef
3.
Travis S: Advances in therapeutic approaches to ulcerative colitis and Crohn's disease. Curr Gastroenterol. 2005, 7 (6): 475-484. 10.1007/s11894-005-0079-9.CrossRef
4.
Neurath M, Fuss I, Strober W: TNBS-colitis. Int Rev Immunol. 2000, 19: 51-62. 10.3109/08830180009048389.PubMedCrossRef
5.
Fujno K, Takami Y, dela Fuente SG, Ludwig KA, Mantyh CR: Inhibition of the vanilloid receptor subtype-1 attenuates TNBS-colitis. J of Gastrointestinal Surg. 2004, 8 (7): 842-848. 10.1016/j.gassur.2004.07.011.CrossRef
6.
Dohi T, Fujihashi K, Rennert PD, Iwatani K, Kiyoto H, McGhee JR: Hapten-induced colitis is associated with colonic patch hypertrophy and T Helper cell-2-type responses. J Exp Med. 1999, 189: 1169-1179. 10.1084/jem.189.8.1169.PubMedPubMedCentralCrossRef
7.
Alex P, Zachos NC, Nguyen T, Gonzales L, Chen TE, Conklin LS, Centola M, Li X: Distinct cytokine patterns identified from multiplex profiles of murine DSS and TNBS-induced colitis. Inflammatory Bowel Diseases. 2008, 15 (3): 341-352. 10.1002/ibd.20753.CrossRef
8.
Zaph C, Troy AE, Taylor BC, Berman-Booty LD, Guild KJ, Du Y, Yost EA, Gruber AD, May MJ, Greten FR, Eckmann L, Karin M, Artis D: Epithelial-cell-intrinsic IKK-β expression regulates intestinal immune homeostasis. Nature. 2007, 446: 552-556. 10.1038/nature05590.PubMedCrossRef
9.
Nenci A, Becker C, Wullaert A, Gareus R, van Loo G, Danese S, Huth M, Nikolaev A, Neufert C, Madison B, Gumucio D, Neurath MF, Pasparakis M: Epithelial NEMO links innate immunity to chronic intestinal inflammation. Nature. 2007, 446: 557-561. 10.1038/nature05698.PubMedCrossRef
10.
Murano M, Maemura K, Hirata I, Toshina K, Nishikawa T, Hamamoto N, Sasaki S, Saitoh O, Katsu K: Therapeutic effect of intracolonically administered nuclear factor kappa B (p65) antisense oligonucleotide on mouse dextran sulphate sodium (DSS)-induced colitis. Clin Exp Immunol. 2000, 120: 51-58. 10.1046/j.1365-2249.2000.01183.x.PubMedPubMedCentralCrossRef
11.
Herfarth H, Brand K, Rath HC, Rogler G, Scholmerich J, Falk W: Nuclear factor-kappa B activity and intestinal inflammation in dextran sulphate sodium (DSS)-induced colitis in mice is suppressed by gliotoxin. Clin Exp Immunol. 2000, 120: 59-65. 10.1046/j.1365-2249.2000.01184.x.PubMedPubMedCentralCrossRef
12.
Fitzpatrick LR, Wang J, Le T: In vitro and in vivo effects of gliotoxin, a fungal metabolite: efficacy against dextran sodium sulfate-induced colitis in rats. Dig Dis Sci. 2000, 45: 2327-2336. 10.1023/A:1005630723111.PubMedCrossRef
13.
Rahman I, Marwick J, Kirkham P: Redox modulation of chromatin remodeling: impact on histone acetylation and deacetylation, NF-κB and pro-inflammatory gene expression. Biochem Pharmacol. 2004, 68 (6): 1255-1267. 10.1016/j.bcp.2004.05.042.PubMedCrossRef
14.
Place RF, Noonan EJ, Giardina C: HDAC inhibition prevents NF-κB activation by suppressing proteasome activity: Down-regulation of proteasome subunit expression stabilizes IκBα. Biochem Pharmacol. 2005, 70: 394-406. 10.1016/j.bcp.2005.04.030.PubMedCrossRef
15.
Siavoshian S, Segain JP, Kornprobst M, Bonnet C, Cherbut C, Galmiche JP, Blottiere HM: Butyrate and trichostatin A effects on the proliferation/differentiation of human intestinal epithelial cells: induction of cyclin D3 and p21 expression. Gut. 2000, 46: 507-514. 10.1136/gut.46.4.507.PubMedPubMedCentralCrossRef
16.
Glauben R, Batra A, Fedke I, Zeitz M, Lehr HA, Leoni F, Mascagni P, Fantuzzi G, Dinarello CA, Siegmund B: Histone hyperacetylation is associated with amelioration of experimental colitis in mice. J Immunol. 2006, 176: 5015-5022.PubMedCrossRef
17.
Roy CC, Kien CL, Bouthillier L, Levy E: Short-chain fatty acids: ready for prime time?. Nutr Clin Pract. 2006, 21 (4): 351-366. 10.1177/0115426506021004351.PubMedCrossRef
18.
Park JS, Lee EJ, Lee JC, Kim WK, Kim HS: Anti-inflammatory effects of short chain fatty acids in IFN-gamma-stimulated RAW 264.7 murine macrophage cells: involvement of NF-kappaB and ERK signalling pathways. Int Immunopharmacol. 2007, 7 (1): 70-77. 10.1016/j.intimp.2006.08.015.PubMedCrossRef
19.
Xu WS, Parmigiani RB, Marks PA: Histone deacetylase inhibitors: molecular mechanisms of action. Oncogene. 2007, 26 (37): 5541-5552. 10.1038/sj.onc.1210620.PubMedCrossRef
20.
Bhavsar P, Ahmad T, Adcock IM: The role of histone deacetylases in asthma and allergic diseases. J Allergy Clin Immunol. 2008, 121 (3): 580-584. 10.1016/j.jaci.2007.12.1156.PubMedCrossRef
21.
Matthews JG, Ito K, Barnes PJ, Adcock IM: Defective glucocorticoid receptor nuclear translocation and altered histone acetylation patterns in glucocorticoid-resistant patients. J Allergy Clin Immunol. 2004, 113: 1100-1108. 10.1016/j.jaci.2004.03.018.PubMedCrossRef
22.
Li L, Leung DYM, Strand MJ, Golevs E: ATF2 impairs glucocorticoid receptor mediated transactivation in human CD8+ T cells. Blood. 2007, 110 (5): 1570-1577. 10.1182/blood-2007-01-070755.PubMedPubMedCentralCrossRef
23.
Fraga MF, Ballestar E, Villar-Garea A, Boix-Chornet M, Espada J, Schotta G, Bonaldi T, Haydon C, Ropero S, Petrie K, Iyer NG, Pérez-Rosado A, Calvo E, Lopez JA, Cano A, Calasanz MJ, Colomer D, Piris MA, Ahn N, Imhof A, Caldas C, Jenuwein T, Esteller M: Loss of acetylation at Lys16 and trimethylation at Lys20 of histone H4 is a common hallmark of human cancer. Nat Gen. 2005, 37 (4): 391-400. 10.1038/ng1531.CrossRef
24.
Morris GP, Beck PL, Herridge MS, Depew WT, Szewczuk MR, Wallace JL: Hapten-induced models of chronic inflammation and ulceration in the rat colon. Gastroenterol. 1989, 96: 795-803.
25.
Vowinkel T, Kalogeris TJ, Mori M, Krieglstein CF, Granger DN: Impact of dextran sulfate sodium load on the severity of inflammation in experimental colitis. Dig Dis Sci. 2004, 49 (4): 556-564. 10.1023/B:DDAS.0000026298.72088.f7.PubMedCrossRef
26.
Ellis RD, Goodlad JR, Limb GA, Powell JJ, Thompson RP, Punchard NA: Activation of nuclear factor kappa B in Crohn's disease. Inflamm Res. 1998, 47: 440-445. 10.1007/s000110050358.PubMedCrossRef
27.
Ito K, Barnes PJ, Adcock IM: Histone acetylation and histone deacetylation. Methods in Molecular Medicine. Asthma: Mechanisms and Protocols. 2000, 44: 309-319.
28.
Ito K, Barnes PJ, Adcock IM: Glucocorticoid receptor recruitment of histone deacetylase 2 inhibits interleukin-1β-induced histone H4 acetylation on lysines 8 and 12. Mol Cell Biol. 2000, 20 (18): 6891-6903. 10.1128/MCB.20.18.6891-6903.2000.PubMedPubMedCentralCrossRef
29.
Ito K, Caramori G, Lim S, Oats T, Chung KF, Barnes PJ, Adcock IM: Expression and activity of histone deacetylases in human asthmatic airways. Am J Respir Crit Care Med. 2002, 166 (3): 392-396. 10.1164/rccm.2110060.PubMedCrossRef
30.
Neurath MF, Finotto S, Fuss I, Boirivant M, Galle PR, Strober W: Regulation of T-cell apoptosis in inflammatory bowel disease: to die or not to die, that is the mucosal question. Trends Immunol. 2001, 22: 21-26. 10.1016/S1471-4906(00)01798-1.PubMedCrossRef
31.
Schreiber S: Inflammatory bowel disease: Immunologic concepts. Hepato-Gastroenterol. 2000, 47: 15-28.
32.
Adcock IM, Cosio B, Tsaprouni L, Barnes PJ, Ito K: Redox regulation of histone deacetylases and glucocorticoid-mediated inhibition of the inflammatory response. Antioxid Redox Signal. 2005, 7 (1-2): 144-152. 10.1089/ars.2005.7.144.PubMedCrossRef
33.
Ito K, Yamamura S, Essilfie-Quaye S, Cosio B, Ito M, Barnes PJ, Adcock IM: Histone deacetylase 2-mediated deacetylation of the glucocorticoid receptor enables NF-kappa B suppression. J Exp Med. 2006, 203 (1): 7-13. 10.1084/jem.20050466.PubMedPubMedCentralCrossRef
34.
Ashburner BP, Westerheide SD, Baldwin AS: The p65 (RelA) subunit of NF-κB interacts with the histone deacetylase (HDAC) corepressors HDAC1 and HDAC2 to negatively regulate gene expression. Molecular and Cellular Biology. 2001, 21: 7065-7077. 10.1128/MCB.21.20.7065-7077.2001.PubMedPubMedCentralCrossRef
35.
Ben-Neriah Y, Schmidt-Supprian M: Epithelial NF-kappaB maintains host gut microflora homeostasis. Nat Immunol. 2007, 8 (5): 479-481. 10.1038/ni0507-479.PubMedCrossRef
36.
Hamer HM, Jonkers D, Venema K, Vanhoutvin S, Troost FJ, Brummer RJ: Review article: the role of butyrate on colonic function. Aliment Pharmacol Ther. 2008, 27 (2): 104-119. 10.1111/j.1365-2036.2007.03562.x.PubMedCrossRef
37.
Maeda S, Hsu LC, Liu H, Bankston LA, Iimura M, Kagnoff MF, Eckmann L, Karin M: Nod2 mutation in Crohn's disease potentiates NF-kappaB activity and IL-1beta processing. Science. 2005, 307 (5710): 734-738. 10.1126/science.1103685.PubMedCrossRef
38.
Vettese-Dadey M, Grant PA, Hebbes TH, Crane-Robinson C, Allis CD, Workman JL: Acetylation of histone H4 plays a primary role in enhancing transcription factor binding to nucleosomal DNA in vitro. EMBO J. 1996, 15 (10): 2508-2518.PubMedPubMedCentral
39.
Nie M, Knox AJ, Pang L: Beta-2 Adrenoreceptor agonists, like glucocorticoids repress eotaxin gene transcription by selective inhibition of histone H4 acetylation. J Immunol. 2005, 175: 478-486.PubMedCrossRef
40.
Elsheikh SE, Green AR, Rakha EA, Powe DG, Ahmed RA, Collins HM, Soria D, Garibaldi JM, Paish CE, Ammar AA, Grainge MJ, Ball GR, Abdelghany MK, Martinez-Pomares L, Heery DM, Ellis IO: Global Histone Modifications in Breast Cancer Correlate with Tumor Phenotypes, Prognostic Factors, and Patient Outcome. Cancer Res. 2009, 69 (9): 3802-3809. 10.1158/0008-5472.CAN-08-3907.PubMedCrossRef
41.
Arts J, Lansink M, Grimbergen J, Toet KH, Kooistra T: Stimulation of tissue-type plasminogen activator gene expression by sodium butyrate and trichostatin A in human endothelial cells involves histone acetylation. Biochem J. 1995, 310: 171-176.PubMedPubMedCentralCrossRef
42.
Song M, Xia B, Li J: Effects of topical treatment of sodium butyrate and 5-aminosalicylic acid on expression of trefoil factor 3, interleukin 1beta, and nuclear factor kappaB in trinitrobenzene sulphonic acid induced colitis in rats. Postgrad Med J. 2006, 82 (964): 130-135. 10.1136/pgmj.2005.037945.PubMedPubMedCentralCrossRef
43.
Chen L, Fischle W, Verdin E, Greene WC: Duration of nuclear NF-kappaB action regulated by reversible acetylation. Science. 2001, 293: 1653-1657. 10.1126/science.1062374.CrossRef
44.
Smoak KA, Cidlowski JA: Mechanisms of glucocorticoid receptor signalling during inflammation. Mechs Age Dev. 2004, 125: 697-706. 10.1016/j.mad.2004.06.010.CrossRef
45.
Hoffmann A, Natoli G, Ghosh S: Transcriptional regulation via the NF-κB signalling module. Oncogene. 2006, 25: 6706-6716. 10.1038/sj.onc.1209933.PubMedCrossRef
46.
Ito K, Lim S, Caramori G, Chung KF, Barnes PJ, Adcock IM: Cigarette smoking reduces histone deacetylase 2 expression, enhances cytokine expression, and inhibits glucocorticoid actions in alveolar macrophages. FASEB J. 2001, 15: 1110-1112.PubMed
47.
Malo MS, Biswas S, Abedrapo MA, Yeh L, Chen A, Hodin RA: The pro-inflammatory cytokines, IL-1β and TNF-α, inhibit intestinal alkaline phosphatase gene expression. DNA and Cell Biology. 2006, 25 (12): 684-695. 10.1089/dna.2006.25.684.PubMedCrossRef
48.
Wang L, Kametani Y, Katano I, Habu S: T-cell specific enhancement of histone H3 acetylation in 5' flanking region of the IL-2 gene. Biochem and Bipophys Commun. 2005, 331 (2): 589-594. 10.1016/j.bbrc.2005.03.216.CrossRef
49.
Letting DL, Rakowski C, Weiss MJ, Blobel GA: Formation of a Tissue-Specific Histone Acetylation Pattern by the Hematopoietic Transcription Factor GATA-1. Mol and Cell Biol. 2003, 23 (4): 1334-1340. 10.1128/MCB.23.4.1334-1340.2003.CrossRef
50.
Wako T, Houben A, Furushima-Shimogawara R, Belyaev ND, Fukui K: Centromere-specific acetylation of histone H4 in barley detected through three-dimensional microscopy. Plant Mol Biol. 2003, 51 (4): 533-541. 10.1023/A:1022375017938.PubMedCrossRef
51.
Quary S, Bizat N, Altairac S, Menetrat H, Mittoux V, Conde F, Hantraye P, Brouillet E: Major strain differences in response to chronic systemic administration of the mitochondrial toxin 3-nitropropionic acid in rats: implications of neuroprotection studies. Neuroscience. 2000, 97: 521-530. 10.1016/S0306-4522(00)00020-8.CrossRef
52.
Jurado F, Bellon JM, Golitsin A, Gimero MJ, Pascual G, Bujan J: Role of macrophages in myocardial apoptosis following cardiac transplant. Influence of immunosuppressive treatment. Histology and Histopathology. 1999, 14: 1033-1043.PubMed
53.
Ejsing-Duun M, Josephsen J, Aasted B, Buschard K, Hansen AK: Dietary Gluten Reduces the Number of Intestinal Regulatory T Cells in Mice. Scandinavian Journal of Immunol. 2008, 67: 553-559. 10.1111/j.1365-3083.2008.02104.x.CrossRef
54.
Shahbazian MD, Grunstein M: Functions of site-specific histone acetylation and deacetylation. Annual Review of Biochem. 2007, 76: 75-100. 10.1146/annurev.biochem.76.052705.162114.CrossRef
55.
Verreault A, Kaufman PD, Kobayashi R, Stillman B: Nucleosome assembly by a complex of CAF-1 and acetylated histones H3/H4. Cell. 1996, 87: 95-104. 10.1016/S0092-8674(00)81326-4.PubMedCrossRef
56.
Liou GG, Tanny JC, Kruger RG, Walz T, Moazed D: Asssembly of the SIR complex and its regulation by O-acetyl-ADP-ribose, a product of NAD-dependent histone deacetylation. Cell. 2005, 121: 515-527. 10.1016/j.cell.2005.03.035.PubMedCrossRef
57.
Hartman HB, Yu J, Alenghat T, Ishizuka T, Lazar MA: The histone binding code of nuclear receptor co-repressors matches the substrate specificity of histone deacetylase 3. EMBO Rep. 2005, 6: 445-451. 10.1038/sj.embor.7400391.PubMedPubMedCentralCrossRef
58.
Wang A, Kurdistani SK, Grunstein M: Requirement of Hos2 histone deacetylase for gene activity in yeast. Science. 2002, 298 (5597): 1412-1414. 10.1126/science.1077790.PubMedCrossRef
59.
Adcock IM, Caramori G: Cross talk between pro-inflammatory transcription factors and glucocorticoids. Immunol and Cell Biol. 2001, 79: 376-384. 10.1046/j.1440-1711.2001.01025.x.CrossRef
60.
Dokmanovic M, Clarke C, Marks PA: Histone deacetylase inhibitors: Overview and perspectives. Mol Cancer Res. 2007, 5 (10): 981-989. 10.1158/1541-7786.MCR-07-0324.PubMedCrossRef
61.
Tao R, de Zoeten EF, Özkaynak E, Chen C, Wang L, Porrett PM, Li B, Turka LA, Olson EN, Greene MI, Wells AD, Hancock WW: Deacetylase inhibition promotes the generation and function of regulatory T cells. Nature Medicine. 2007, 13 (11): 1299-1307. 10.1038/nm1652.PubMedCrossRef
62.
Tsuji NM, Mizumachi K, Kurisaki J: Interleukin-10-secreting Peyer's patch cells are responsible for active suppression in low-dose oral tolerance. Immunology. 2001, 103 (4): 458-464. 10.1046/j.1365-2567.2001.01265.x.PubMedPubMedCentralCrossRef
63.
Ma X, Ezzeldin HH, Diasio RB: Histone deacetylase inhibitors: Current status and overview of recent clinical trials. Drugs. 2009, 69 (14): 1911-1934. 10.2165/11315680-000000000-00000.PubMedCrossRef
Metadata
Title
Differential patterns of histone acetylation in inflammatory bowel diseases
Authors
Loukia G Tsaprouni
Kazuhiro Ito
Jonathan J Powell
Ian M Adcock
Neville Punchard
Publication date
01-12-2011
Publisher
BioMed Central
Published in
Journal of Inflammation / Issue 1/2011
Electronic ISSN: 1476-9255
DOI
https://doi.org/10.1186/1476-9255-8-1

Other articles of this Issue 1/2011

Journal of Inflammation 1/2011 Go to the issue

Research

Ageing prolongs inflammatory marker expression in regenerating rat skeletal muscles after injury

Research

Elevated salivary C-reactive protein levels are associated with active and passive smoking in healthy youth: A pilot study

Research

Attenuating effect of pretreatment with Yiqifumai on lipopolysaccharide-induced intestine injury and survival rate in rat

Research

Cytokine & chemokine response in the lungs, pleural fluid and serum in thoracic surgery using one-lung ventilation

Review

Role of IL-33 in inflammation and disease

Research

Antioxidant and potential anti-inflammatory activity of extracts and formulations of white tea, rose, and witch hazel on primary human dermal fibroblast cells
Obesity Clinical Trial Summary

At a glance: The STEP trials

Read more

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Highlights from the ACC 2024 Congress

Year in Review: Pediatric cardiology

Pediatric Cardiology Video

Watch Dr. Anne Marie Valente present the last year's highlights in pediatric and congenital heart disease in the official ACC.24 Year in Review session.

Year in Review: Pulmonary vascular disease

Cardiopulmonary Comorbidity Video

The last year's highlights in pulmonary vascular disease are presented by Dr. Jane Leopold in this official video from ACC.24.

Year in Review: Valvular heart disease

Valvular Heart Disease Video

Watch Prof. William Zoghbi present the last year's highlights in valvular heart disease from the official ACC.24 Year in Review session.

Year in Review: Heart failure and cardiomyopathies

Heart Failure Video

Watch this official video from ACC.24. Dr. Biykem Bozkurt discuss last year's major advances in heart failure and cardiomyopathies.

ACC 2024 Congress Coverage

Heart Failure Video

Year in Review: Heart failure and cardiomyopathies

Watch now

Watch this official video from ACC.24. Dr. Biykem Bozkurt discuss last year's major advances in heart failure and cardiomyopathies.

Semaglutide benefits people with type 2 diabetes and obesity-related heart failure

16-04-2024 Type 2 Diabetes News

Incentivised to exercise

11-04-2024 Lifestyle Modifications News

New intervention for STEMI-related cardiogenic shock

10-04-2024 Myocardial Infarction News

» View more highlights on the ACC 2024 congress hub page

Image Credits