Epigenetic regulation of established human type 1 versus type 2 cytokine responses

Su, Ruey-Chyi; Becker, Allan B.; Kozyrskyj, Anita L.; HayGlass, Kent T.

doi:10.1016/j.jaci.2007.09.004

Cited by 73 publications

(64 citation statements)

References 45 publications

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“…Herein, we have identified an epigenetic mechanism that regulates their activation by IL-13, a key cytokine involved in allergic inflammation (46 -49). To the best of our knowledge, this is the first time that IL-13 has been shown to operate by modulating histone acetylation, although IL-13 induction itself has been shown to be increased by histone deacetylase inhibition in a preliminary report (50).…”

Section: Discussionmentioning

confidence: 82%

Epigenetic Regulation of the IL-13-induced Human Eotaxin-3 Gene by CREB-binding Protein-mediated Histone 3 Acetylation

Lim¹,

Blanchard³

et al. 2011

Journal of Biological Chemistry

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The etiology of a variety of chronic inflammatory disorders has been attributed to the interaction of genetic and environmental factors. Herein, we identified a link between epigenetic regulation and IL-13-driven eotaxin-3 in the pathogenesis of chronic allergic inflammation. We first demonstrated that the cAMP-responsive element (CRE) site in the eotaxin-3 promoter affects IL-13-induced eotaxin-3 promoter activity. Furthermore, the CRE-binding protein-binding protein (CBP), a histone acetyltransferase, induced base-line and IL-13-induced eotaxin-3 promoter activity. Additionally, IL-13 treatment promoted global histone 3 acetylation as well as the formation of a complex containing CBP and STAT6 and the subsequent acetylation of histone 3 at the eotaxin-3 promoter. CBP gene silencing decreased IL-13-induced transcription of eotaxin-3. Conversely, inhibition of histone deacetylation increased IL-13-induced eotaxin-3 production. Clinical studies demonstrated markedly increased global acetylation of histone 3 in the inflamed tissue of patients with allergic inflammation. Collectively, these results identify an epigenetic mechanism involving CBP and chromatin remodeling in regulating IL-13-induced chemokine transcription.

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Section: Discussionmentioning

confidence: 82%

Epigenetic Regulation of the IL-13-induced Human Eotaxin-3 Gene by CREB-binding Protein-mediated Histone 3 Acetylation

Lim¹,

Blanchard³

et al. 2011

Journal of Biological Chemistry

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“…Reviewed in (79) Improved survival after hemorrhage (89) Decreased cytokinemia after systemic endotoxin (10,11,136) Decreased NO production (6,10,32) Protection against hepatitis after intravenous concanavalin A (11) Suppression of vascular cell adhesion molecule-1 expression (137) In vitro cytokine production Decreased gene expression and synthesis of LPS-induced TNFα and IFNγ in human peripheral blood mononuclear cells (10,11,138) Decreased IL-1β-induced IL-6 in synovial cells and human blood monocytes (23) Reduced IFNγ in mouse trophoblasts (139) Decreased production of IL-6 in PBMCs stimulated with IL-12 plus IL-18 (11) Decreased secretion of IL-1β (10,11,52) Decreased IL-12 and IL-17 production from monocytes and dendritic cells (10,20,50) Decreased IL-6 from stromal cells (104) Reduced IL-1β-induced PGE2 and NO in human chrondrocytes (140) Decreased ischemia-induced retinal TNFα production (141) Downregulation of IL-12 transcription in transformed lung epithelial cells (142) Increased PGD2 production and suppression of matrix metalloproteinases (82) Suppression of c-jun and transcription of COX-2 (83)…”

Section: Systemic Inflammationmentioning

confidence: 99%

Histone Deacetylase Inhibitors for Treating a Spectrum of Diseases Not Related to Cancer

Dinarello

Fossati

Mascagni

2011

Mol Med

137

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This issue of Molecular Medicine contains 14 original research reports and state-of-the-art reviews on histone deacetylase inhibitors (HDACi's), which are being studied in models of a broad range of diseases not related to the proapoptotic properties used to treat cancer. The spectrum of these diseases responsive to HDACi's is for the most part due to several antiinflammatory properties, often observed in vitro but importantly also in animal models. One unifying property is a reduction in cytokine production as well as inhibition of cytokine postreceptor signaling. Distinct from their use in cancer, the reduction in inflammation by HDACi's is consistently observed at low concentrations compared with the higher concentrations required for killing tumor cells. This characteristic makes HDACi's attractive candidates for treating chronic diseases, since low doses are well tolerated. For example, low oral doses of the HDACi givinostat have been used in children to reduce arthritis and are well tolerated. In addition to the antiinflammatory properties, HDACi's have shown promise in models of neurodegenerative disorders, and HDACi's also hold promise to drive HIV-1 out of latently infected cells. No one molecular mechanism accounts for the non-cancer-related properties of HDACi's, since there are 18 genes coding for histone deacetylases. Rather, there are mechanisms unique for the pathological process of specific cell types. In this overview, we summarize the preclinical data on HDACi's for therapy in a wide spectrum of diseases unrelated to the treatment of cancer. The data suggest the use of HDACi's in treating autoimmune as well as chronic inflammatory diseases.

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“…There is evidence that acetylation of histones is relevant to the maintenance of T-cell differentiation and that skewing of the cytokine profile of T cells towards a Th2 bias is crucially dependent on the activity of histone deacetylase (HDAC) (Su et al, 2008). The importance of HDAC as a potential therapeutic target has recently been demonstrated elegantly in a mouse model of Huntington's disease, in which chronic administration of HDAC inhibitors ameliorated disease manifestations (Thomas et al, 2008).…”

Section: Meddling With Epigeneticsmentioning

confidence: 99%

“…Presumably there is some merit in the inverse inference, namely that modification of the diet of a pregnant mother might, through epigenetic mechanisms, be able to diminish the severity or likelihood of development of asthma in her child. The impact of dietary modification, both prenatally and during early childhood, is a potentially fruitful area for further research.There is evidence that acetylation of histones is relevant to the maintenance of T-cell differentiation and that skewing of the cytokine profile of T cells towards a Th2 bias is crucially dependent on the activity of histone deacetylase (HDAC) (Su et al, 2008). The importance of HDAC as a potential therapeutic target has recently been demonstrated elegantly in a mouse model of Huntington's disease, in which chronic administration of HDAC inhibitors ameliorated disease manifestations (Thomas et al, 2008).…”

mentioning

confidence: 99%

Epigenetic changes in childhood asthma

Kumar

Hitchins

Foster

2009

Disease Models &Amp; Mechanisms

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Two novel conceptual frameworks have captured the imagination of biomedical scientists who are interested in the pathogenesis of chronic and complex diseases. One is epigenetics, which may explain how environmental factors can cause stable alterations in phenotype without changes in genotype. The other is transcriptional regulation by microRNA. In this Commentary, we examine the relevance of epigenetics and the role of microRNA in the induction and progression of asthma in childhood, and propose a model to link these mechanisms. Childhood asthmaAsthma is one of the most common chronic diseases affecting children, especially in economically developed nations. For example, in Australia the prevalence of asthma is 9-11% in the 2-4-year-old age group and 12-16% in the 5-17-year-old age group, with males affected more commonly than females (Ampon et al., 2007). Childhood asthma is linked strongly to atopy, which is a genetic predisposition to produce immunoglobulin E (IgE) antibodies in response to ordinary exposures to environmental allergens, and is often associated with symptoms of asthma, rhinoconjunctivitis or eczema (Johansson et al., 2004). In turn, atopy is associated characteristically with a T helper 2 (Th2)-biased immunological response (Bacharier et al., 2008). However, the pathogenesis of this illness remains incompletely understood. Both genetic predisposition and various environmental factors clearly play important roles in the development of allergic asthma (Sly et al., 2008), but the relative importance of these various contributory mechanisms and the ways in which they might interact are difficult to assess.Epidemiological studies strongly suggest that the most important environmental factors that predispose to the development of asthma are lower respiratory tract viral infections associated with wheezing, especially in early childhood, and repeated inhalation exposure to allergens, which appear to be synergistic (Holt and Sly, 2007;Sly et al., 2008). The role of early-life viral infections is somewhat controversial because the so-called 'hygiene hypothesis' proposed that infections in early childhood, which are acquired by contact with older siblings or other children, might protect against subsequent development of asthma and other allergic diseases (reviewed by Wong and Chow, 2008). However, a recent longitudinal study involving prospective follow-up to 8 years of age strongly suggests that this is unlikely to be a valid notion (Caudri et al., 2009). Among the early-life viral infections, respiratory syncytial virus (RSV) and rhinovirus are of particular interest, because wheezing lower respiratory tract infections in the first year of life are associated strongly with subsequent development of asthma (Kristjansson et al., 2005;Sigurs et al., 2005; Kusel et al., 2007;Jackson et al., 2008; Mohapatra and Boyapalle, 2008). Other clearly defined risk factors are exposure to airborne environmental irritants such as tobacco smoke and traffic pollutants: evidence for their role comes from numerous larg...

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Epigenetic regulation of established human type 1 versus type 2 cytokine responses

Cited by 73 publications

References 45 publications

Epigenetic Regulation of the IL-13-induced Human Eotaxin-3 Gene by CREB-binding Protein-mediated Histone 3 Acetylation

Epigenetic Regulation of the IL-13-induced Human Eotaxin-3 Gene by CREB-binding Protein-mediated Histone 3 Acetylation

Histone Deacetylase Inhibitors for Treating a Spectrum of Diseases Not Related to Cancer

Epigenetic changes in childhood asthma

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