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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.


Related in: MedlinePlus

Acetylation on histone 4 in the trinitrobenzene sulfonic acid (TNBS) rat model of inflammation. A: Sham (saline treated) operated and TNBS treated rat large intestine. Rats were Sham or TNBS treated for 7 days before sacrifice. Well-advanced inflammation is apparent in the colon of the TNBS rat model. B: Pan acetylation on histone 4 (H4). The Sham model was saline-treated and therefore less inflamed (control). Results were obtained by Western blotting. The ratio of the density of histone H4 bands over β-actin control bands was calculated. In order to evaluate changes in density from different Western blotting experiments control densitometry was denoted as 100% and differences were accounted as increase percentage of the control. Representative examples of bands obtained are also illustrated. Columns represent the densitometric evaluation of three independent experiments (mean ± SEM). (*p < 0.05 vs Sham proximal or Sham distal respectively).
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Figure 1: Acetylation on histone 4 in the trinitrobenzene sulfonic acid (TNBS) rat model of inflammation. A: Sham (saline treated) operated and TNBS treated rat large intestine. Rats were Sham or TNBS treated for 7 days before sacrifice. Well-advanced inflammation is apparent in the colon of the TNBS rat model. B: Pan acetylation on histone 4 (H4). The Sham model was saline-treated and therefore less inflamed (control). Results were obtained by Western blotting. The ratio of the density of histone H4 bands over β-actin control bands was calculated. In order to evaluate changes in density from different Western blotting experiments control densitometry was denoted as 100% and differences were accounted as increase percentage of the control. Representative examples of bands obtained are also illustrated. Columns represent the densitometric evaluation of three independent experiments (mean ± SEM). (*p < 0.05 vs Sham proximal or Sham distal respectively).

Mentions: TNBS induced significant inflammation within the proximal and distal regions of the colon although the extent of inflammation was greater in the distal region (Figure 1A).


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 histone 4 in the trinitrobenzene sulfonic acid (TNBS) rat model of inflammation. A: Sham (saline treated) operated and TNBS treated rat large intestine. Rats were Sham or TNBS treated for 7 days before sacrifice. Well-advanced inflammation is apparent in the colon of the TNBS rat model. B: Pan acetylation on histone 4 (H4). The Sham model was saline-treated and therefore less inflamed (control). Results were obtained by Western blotting. The ratio of the density of histone H4 bands over β-actin control bands was calculated. In order to evaluate changes in density from different Western blotting experiments control densitometry was denoted as 100% and differences were accounted as increase percentage of the control. Representative examples of bands obtained are also illustrated. Columns represent the densitometric evaluation of three independent experiments (mean ± SEM). (*p < 0.05 vs Sham proximal or Sham distal respectively).
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 1: Acetylation on histone 4 in the trinitrobenzene sulfonic acid (TNBS) rat model of inflammation. A: Sham (saline treated) operated and TNBS treated rat large intestine. Rats were Sham or TNBS treated for 7 days before sacrifice. Well-advanced inflammation is apparent in the colon of the TNBS rat model. B: Pan acetylation on histone 4 (H4). The Sham model was saline-treated and therefore less inflamed (control). Results were obtained by Western blotting. The ratio of the density of histone H4 bands over β-actin control bands was calculated. In order to evaluate changes in density from different Western blotting experiments control densitometry was denoted as 100% and differences were accounted as increase percentage of the control. Representative examples of bands obtained are also illustrated. Columns represent the densitometric evaluation of three independent experiments (mean ± SEM). (*p < 0.05 vs Sham proximal or Sham distal respectively).
Mentions: TNBS induced significant inflammation within the proximal and distal regions of the colon although the extent of inflammation was greater in the distal region (Figure 1A).

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