3 replies to this topic

[youandme]

Deacetylase inhibition promotes the generation and function of regulatory T cells.
Tao R, de Zoeten EF, Ozkaynak E, Chen C, Wang L, Porrett PM, Li B, Turka LA, Olson EN, Greene MI, Wells AD, Hancock WW. Division of Transplantation Immunology, Department of Pathology and Laboratory Medicine and Biesecker Center for Studies of Pediatric Liver Diseases, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania 19104-4318, USA.

Histone/protein deacetylases (HDACs) regulate chromatin remodeling and gene expression as well as the functions of more than 50 transcription factors and nonhistone proteins. We found that administration of an HDAC inhibitor (HDACi) in vivo increased Foxp3 gene expression, as well as the production and suppressive function of regulatory T cells (T(reg) cells). Although T(reg) cells express multiple HDACs, HDAC9 proved particularly important in regulating Foxp3-dependent suppression. Optimal T(reg) function required acetylation of several lysines in the forkhead domain of Foxp3, and Foxp3 acetylation enhanced binding of Foxp3 to the Il2 promoter and suppressed endogenous IL-2 production. HDACi therapy in vivo enhanced T(reg)-mediated suppression of homeostatic proliferation, decreased inflammatory bowel disease through T(reg)-dependent effects, and, in conjunction with a short course of low-dose rapamycin, induced permanent, T(reg)-dependent cardiac and islet allograft survival and donor-specific allograft tolerance. Our data show that use of HDACi allows the beneficial pharmacologic enhancement of both the numbers and suppressive function of Foxp3(+) T(reg) cells.





Using histone deacetylase inhibitors to enhance Foxp3(+) regulatory T-cell function and induce allograft tolerance.
Wang L, Tao R, Hancock WW. Department of Pathology and Laboratory Medicine, Stokes Research Institute and Biesecker Pediatric Liver Center, Children's Hospital of Philadelphia, University of Pennsylvania, Philadelphia, PA 19104-4318, USA.

The histone/protein deacetylase inhibitor (HDACi), trichostatin A (TsA), increases the production and suppressive function of Foxp3(+) regulatory T cells (T(regs)), at least in part, by promoting the acetylation of Foxp3 protein itself. Acetylation of Foxp3 is required for effective binding of Foxp3 to the promoter of the interleukin-2 (IL-2) gene and the suppression of IL-2 expression. We have sought to identify agents that had similar effects on T(regs), but without the associated toxicity of TsA. This review summarizes the contrasting effects of various HDACis on T(reg) functions in vitro and in vivo. Agents that block primarily class I HDAC had minimal or no effect on T(reg) suppression, whereas multiple inhibitors of both class I and class II HDAC enhanced T(reg) suppression in vitro and in vivo. These data indicate tools for further analysis of T(reg) functions, and point to a critical role of class II HDAC in the regulation of T(regs). Such knowledge has direct implications for the development of in vivo approaches to treat autoimmune and other inflammatory diseases.







Anyone know of further studies...?

Also looking for Dietary or supplemental HDAC inhibitors...with evidence of enhancing Treg's..




Cheers

[youandme]

Dietary histone deacetylase inhibitors
Broccoli Sprouts !...

Anyone know for sure which classes of HDAC Broccoli Inhibits ?

http://www.ncbi.nlm....les/PMC2737738/

Dietary histone deacetylase inhibitorsFrom cells to mice to manRoderick H. Dashwood^a* and Emily Ho^baLinus Pauling Institute, Department of Environmental & Molecular Toxicology, Oregon State University, Corvallis, OR 97331, USA^bLinus Pauling Institute, Department of Nutrition & Exercise Sciences, Oregon State University, Corvallis, OR 97331, USA^*Corresponding author. Tel.: +1 541 737 5086; fax: +1 541 737 5077. E-mail address: Rod.Dashwood@oregonstate.edu (R.H. Dashwood).

• Other Sections▼
• Abstract
• 1. HDAC inhibitors in cancer prevention and therapy
• 2. HDAC inhibition in cancer cells
• 3. HDAC inhibition in mice
• 4. HDAC inhibition in man
• 5. Implications of HDAC inhibitors in the diet
• References

AbstractSulforaphane (SFN) is an isothiocyanate found in cruciferous vegetables, such as broccoli and broccoli sprouts. This anticarcinogen was first identified as a potent inducer of Phase 2 detoxification enzymes, but evidence is mounting that SFN also acts through epigenetic mechanisms. SFN has been shown to inhibit histone deacetylase (HDAC) activity in human colon and prostate cancer lines, with an increase in global and local histone acetylation status, such as on the promoter regions of P21 and bax genes. SFN also inhibited the growth of prostate cancer xenografts and spontaneous intestinal polyps in mouse models, with evidence for altered histone acetylation and HDAC activities in vivo. In human subjects, a single ingestion of 68 g broccoli sprouts inhibited HDAC activity in circulating peripheral blood mononuclear cells 3-6 h after consumption, with concomitant induction of histone H3 and H4 acetylation. These findings provide evidence that one mechanism of cancer chemoprevention by SFN is via epigenetic changes associated with inhibition of HDAC activity. Other dietary agents such as butyrate, biotin, lipoic acid, garlic organosulfur compounds, and metabolites of vitamin E have structural features compatible with HDAC inhibition. The ability of dietary compounds to de-repress epigenetically silenced genes in cancer cells, and to activate these genes in normal cells, has important implications for cancer prevention and therapy. In a broader context, there is growing interest in dietary HDAC inhibitors and their impact on epigenetic mechanisms affecting other chronic conditions, such as cardiovascular disease, neurodegeneration and aging.

Edited by youandme, 18 October 2009 - 11:42 AM.

[tunt01]

resveratrol is a class III HDACi which has an impact on t-cell function.

[youandme]

resveratrol is a class III HDACi which has an impact on t-cell function.

Hi Prophets
Please if you have any links to HDACi (Resveratrol) for Class III please post.
TIA