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Differential patterns of histone acetylation in inflammatory bowel diseases.

Tsaprouni LG, Ito K, Powell JJ, Adcock IM, Punchard N - J Inflamm (Lond) (2011)

Bottom Line: Post-translational modifications of histones, particularly acetylation, are associated with the regulation of inflammatory gene expression.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.These results demonstrate that histone acetylation is associated with inflammation and may provide a novel therapeutic target for mucosal inflammation.

View Article: PubMed Central - HTML - PubMed

Affiliation: Airways Disease Section, National Heart & Lung Institute, Imperial College London, Dovehouse Street, London, SW3 6LY, UK. ian.adcock@imperial.ac.uk.

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.

No MeSH data available.


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Acetylation on histones 3 (H3) and 4 (H4) in Lewis and Sprague-Dawley dextran sulfate sodium (5% DSS) treated rats. Tissue samples were obtained from the sigmoid colon of the animals. A: Representative bands of H4 and H3 acetylation as obtained by Western blotting. β-actin levels were measured to ensure equal protein loading. The results are representative of three independent experiments. B, C: Graphical analysis of data Lanes represent: (1) non-DSS treated Lewis rats (control), (2) DSS-treated Lewis rats, (3) non-DSS treated Sprague-Dawley rats (control) (4) DSS-treated Sprague-Dawley rats. Columns represent the mean ± SEM of three independent experiments (*p < 0.05). D: Histone 3 (H3) and histone 4 (H4) localisation in Peyer's patches of dextran sulfate sodium (DSS) treated Lewis rats. H3 is acetylated mainly in the mantle zone and H4 is acetylated throughout the surface of Peyer's patches to both mantle zone and germinal centre cells. In Peyer's patches of untreated animals no acetylation on either histone 3 or 4 was apparent. Micrographs are representative of two individual experiments for each strain. Isotype controls show no staining.
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Figure 3: Acetylation on histones 3 (H3) and 4 (H4) in Lewis and Sprague-Dawley dextran sulfate sodium (5% DSS) treated rats. Tissue samples were obtained from the sigmoid colon of the animals. A: Representative bands of H4 and H3 acetylation as obtained by Western blotting. β-actin levels were measured to ensure equal protein loading. The results are representative of three independent experiments. B, C: Graphical analysis of data Lanes represent: (1) non-DSS treated Lewis rats (control), (2) DSS-treated Lewis rats, (3) non-DSS treated Sprague-Dawley rats (control) (4) DSS-treated Sprague-Dawley rats. Columns represent the mean ± SEM of three independent experiments (*p < 0.05). D: Histone 3 (H3) and histone 4 (H4) localisation in Peyer's patches of dextran sulfate sodium (DSS) treated Lewis rats. H3 is acetylated mainly in the mantle zone and H4 is acetylated throughout the surface of Peyer's patches to both mantle zone and germinal centre cells. In Peyer's patches of untreated animals no acetylation on either histone 3 or 4 was apparent. Micrographs are representative of two individual experiments for each strain. Isotype controls show no staining.

Mentions: Acetylation of both histones 4 and 3 was evident in non-DSS treated rats but this was enhanced in all inflamed areas, regardless of distinct positions in the colon, of both for Lewis rats (H4: 222 ± 31 DSS treated vs 100 ± 31% non-DSS treated animals, p < 0.05; H3 292 ± 40 DSS treated vs 100 ± 13% non-DSS treated animals, p < 0.05) and Spraque-Dawley rats (H4: 187 ± 30 DSS treated vs 100 ± 21% non-DSS treated animals, p < 0.05; H3 361 ± 36 DSS treated vs 100 ± 15% non-DSS treated animals, p < 0.05) (Figure 3). Similar results were obtained from Sprague-Dawley DSS-treated cells.


Differential patterns of histone acetylation in inflammatory bowel diseases.

Tsaprouni LG, Ito K, Powell JJ, Adcock IM, Punchard N - J Inflamm (Lond) (2011)

Acetylation on histones 3 (H3) and 4 (H4) in Lewis and Sprague-Dawley dextran sulfate sodium (5% DSS) treated rats. Tissue samples were obtained from the sigmoid colon of the animals. A: Representative bands of H4 and H3 acetylation as obtained by Western blotting. β-actin levels were measured to ensure equal protein loading. The results are representative of three independent experiments. B, C: Graphical analysis of data Lanes represent: (1) non-DSS treated Lewis rats (control), (2) DSS-treated Lewis rats, (3) non-DSS treated Sprague-Dawley rats (control) (4) DSS-treated Sprague-Dawley rats. Columns represent the mean ± SEM of three independent experiments (*p < 0.05). D: Histone 3 (H3) and histone 4 (H4) localisation in Peyer's patches of dextran sulfate sodium (DSS) treated Lewis rats. H3 is acetylated mainly in the mantle zone and H4 is acetylated throughout the surface of Peyer's patches to both mantle zone and germinal centre cells. In Peyer's patches of untreated animals no acetylation on either histone 3 or 4 was apparent. Micrographs are representative of two individual experiments for each strain. Isotype controls show no staining.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3040698&req=5

Figure 3: Acetylation on histones 3 (H3) and 4 (H4) in Lewis and Sprague-Dawley dextran sulfate sodium (5% DSS) treated rats. Tissue samples were obtained from the sigmoid colon of the animals. A: Representative bands of H4 and H3 acetylation as obtained by Western blotting. β-actin levels were measured to ensure equal protein loading. The results are representative of three independent experiments. B, C: Graphical analysis of data Lanes represent: (1) non-DSS treated Lewis rats (control), (2) DSS-treated Lewis rats, (3) non-DSS treated Sprague-Dawley rats (control) (4) DSS-treated Sprague-Dawley rats. Columns represent the mean ± SEM of three independent experiments (*p < 0.05). D: Histone 3 (H3) and histone 4 (H4) localisation in Peyer's patches of dextran sulfate sodium (DSS) treated Lewis rats. H3 is acetylated mainly in the mantle zone and H4 is acetylated throughout the surface of Peyer's patches to both mantle zone and germinal centre cells. In Peyer's patches of untreated animals no acetylation on either histone 3 or 4 was apparent. Micrographs are representative of two individual experiments for each strain. Isotype controls show no staining.
Mentions: Acetylation of both histones 4 and 3 was evident in non-DSS treated rats but this was enhanced in all inflamed areas, regardless of distinct positions in the colon, of both for Lewis rats (H4: 222 ± 31 DSS treated vs 100 ± 31% non-DSS treated animals, p < 0.05; H3 292 ± 40 DSS treated vs 100 ± 13% non-DSS treated animals, p < 0.05) and Spraque-Dawley rats (H4: 187 ± 30 DSS treated vs 100 ± 21% non-DSS treated animals, p < 0.05; H3 361 ± 36 DSS treated vs 100 ± 15% non-DSS treated animals, p < 0.05) (Figure 3). Similar results were obtained from Sprague-Dawley DSS-treated cells.

Bottom Line: Post-translational modifications of histones, particularly acetylation, are associated with the regulation of inflammatory gene expression.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.These results demonstrate that histone acetylation is associated with inflammation and may provide a novel therapeutic target for mucosal inflammation.

View Article: PubMed Central - HTML - PubMed

Affiliation: Airways Disease Section, National Heart & Lung Institute, Imperial College London, Dovehouse Street, London, SW3 6LY, UK. ian.adcock@imperial.ac.uk.

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.

No MeSH data available.


Related in: MedlinePlus