Regulation of microglial inflammatory response by histone deacetylase inhibitors

Suuronen, Tiina; Huuskonen, Juhani; Pihlaja, Rea; Kyrylenko, Sergiy; Salminen, Antero

doi:10.1046/j.1471-4159.2003.02004.x

Cited by 108 publications

(97 citation statements)

References 47 publications

(122 reference statements)

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“…As reviewed in other sections of this issue of Molecular Medicine, HDAC inhibition modifies innate and adaptive immune responses (42)(43)(44)(45). The specific impact of HDACi on the immune system in relation to T1D and T2D is underinvestigated.…”

Section: Innate and Adaptive Immune Systems And Hdaci In Diabetesmentioning

confidence: 99%

Histone Deacetylase (HDAC) Inhibition as a Novel Treatment for Diabetes Mellitus

Christensen

Dahllöf

Lundh

et al. 2011

Mol Med

230

167

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Both common forms of diabetes have an inflammatory pathogenesis in which immune and metabolic factors converge on interleukin-1β as a key mediator of insulin resistance and β-cell failure. In addition to improving insulin resistance and preventing β-cell inflammatory damage, there is evidence of genetic association between diabetes and histone deacetylases (HDACs); and HDAC inhibitors (HDACi) promote β-cell development, proliferation, differentiation and function and positively affect late diabetic microvascular complications. Here we review this evidence and propose that there is a strong rationale for preclinical studies and clinical trials with the aim of testing the utility of HDACi as a novel therapy for diabetes.

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Section: Innate and Adaptive Immune Systems And Hdaci In Diabetesmentioning

confidence: 99%

Histone Deacetylase (HDAC) Inhibition as a Novel Treatment for Diabetes Mellitus

Christensen

Dahllöf

Lundh

et al. 2011

Mol Med

230

167

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“…Effects can differ extensively, or even be opposed e.g., in microglial cells versus macrophages. 98,99 In general, the administration of either HDACi, VPA, or SB, leads to a significant suppression of microglia activation 47,53,100 and additionally to the inhibition of further inflammatory markers like monocytes and macrophages in stroke. 47 On the gene level, HDAC inhibition impacts the expression of heat shock protein (HSP)70, a heat shock/stress protein that assists proper protein folding, and is involved in inflammatory processes.…”

Section: Excitotoxicitymentioning

confidence: 99%

Epigenetic Mechanisms in Cerebral Ischemia

Schweizer

Meisel

Märschenz

2013

J Cereb Blood Flow Metab

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Treatment efficacy for ischemic stroke represents a major challenge. Despite fundamental advances in the understanding of stroke etiology, therapeutic options to improve functional recovery remain limited. However, growing knowledge in the field of epigenetics has dramatically changed our understanding of gene regulation in the last few decades. According to the knowledge gained from animal models, the manipulation of epigenetic players emerges as a highly promising possibility to target diverse neurologic pathologies, including ischemia. By altering transcriptional regulation, epigenetic modifiers can exert influence on all known pathways involved in the complex course of ischemic disease development. Beneficial transcriptional effects range from attenuation of cell death, suppression of inflammatory processes, and enhanced blood flow, to the stimulation of repair mechanisms and increased plasticity. Most striking are the results obtained from pharmacological inhibition of histone deacetylation in animal models of stroke. Multiple studies suggest high remedial qualities even upon late administration of histone deacetylase inhibitors (HDACi). In this review, the role of epigenetic mechanisms, including histone modifications as well as DNA methylation, is discussed in the context of known ischemic pathways of damage, protection, and regeneration.

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“…TLR4/NF-κB controls the expression of many inflammatory genes (Fig. 1C) and so it makes sense that it can serve as a control point for limiting the IR (Suuronen et al, 2003). Indeed, several studies have reported a decrease in the TLR4/NF-κB response to LPS following butyrate administration (Huuskonen et al, 2004;Wu et al, 2012).…”

Section: Gene Expression and Pathway Analysismentioning

confidence: 99%

Butyrate-Mediated Genomic Changes Involved in Non-Specific Host Defenses, Matrix Remodeling and the Immune Response in the Rumen Epithelium of Cows Afflicted With Subacute Ruminal Acidosis

Dionissopoulos

Laarman

AlZahal

et al. 2013

American Journal of Animal and Veterinary Sciences

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Subacute Ruminal Acidosis (SARA) is a disorder in cattle which can lead to chronic inflammation in the rumen epithelium, known as rumenitis. Butyrate has been shown to attenuate some of the detrimental effects of inflammatory gastroenteral disorders but the molecular mechanisms mediated by butyrate have not been defined. The objective of this study was to define the inflammatory-related genomic changes responsible for the beneficial effects of butyrate. Experimentally, 16 fistulated dairy cows at mid-lactation were fed a SARA-inducing (45% non-fiber carbohydrate) diet beginning 2 days before the beginning of treatment and continuing throughout the experiment. Cows were then evenly divided into treatment groups where a carrier with (n = 8) or without (n = 8) supplemental butyrate (2.5% initial DM intake) was deposited into the rumen daily for 7 days. The minimum rumen pH was higher in cows with supplemental butyrate (4.96±0.09 to 5.20±0.05, p = 0.040), but mean pH, maximum pH and the duration for which rumen pH was below 5.6 was unaffected. Free plasma Lipopolysaccharide (LPS) concentration was unaffected by treatment as was the concentration of Serum Amyloid A (SAA), although the LPS Binding Protein (LBP) concentration was increased by the addition of butyrate to the rumen (6.91±0.29 to 7.93±0.29 µg mL −1 , p = 0.024). Of the rumen Short Chain Fatty Acids (SCFA) tested, only butyrate showed a pronounced treatment effect, rising from 8.60±0.94 to 21.60±0.94 mM (p≤0.0001). Plasma Beta-Hydroxybutyrate (BHBA) concentration also increased (799.50±265.24 to 3261.63±265.24 µM, p≤0.001). Butyrate infusion did not affect milk parameters (total fat, lactose, total protein and LOS); however, when related to dry matter intake, milk production efficiency was increased (p = 0.035). Microarray and qRT-PCR analyses of rumen papillae biopsies collected on day 7 found that butyrate administration affected (p≤0.05) the expression of genes involved in Non-Specific Host Defense (NSHD), Remodeling or adaptation (RM) and Immune Response (IR). Of the 49 genes tested by qRT-PCR, 9 (LCN2, MMP1, MUC16, GPX2, CSTA, FUT1, SERPINE2, BCAM, RAC3) were upregulated, 20 (MTOR, AKIRIN2, NFKBIZ, NFKB2, ACVR2A, LAMB1, FRS2, PPARD, LBP, NEDD4L, SGK1, DEDD2, MAP3K8, PARD6B, PLIN2, ADA, HPGD, FMO5, BMP6, TCHH) were downregulated and 20 were unchanged due to butyrate administration in the proximal gastrointestinal tract. AJAVSThese results demonstrate the potential protective effect and molecular mechanisms involved in a novel butyrate treatment for inflammatory gastrointestinal conditions.

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Regulation of microglial inflammatory response by histone deacetylase inhibitors

Cited by 108 publications

References 47 publications

Histone Deacetylase (HDAC) Inhibition as a Novel Treatment for Diabetes Mellitus

Histone Deacetylase (HDAC) Inhibition as a Novel Treatment for Diabetes Mellitus

Epigenetic Mechanisms in Cerebral Ischemia

Butyrate-Mediated Genomic Changes Involved in Non-Specific Host Defenses, Matrix Remodeling and the Immune Response in the Rumen Epithelium of Cows Afflicted With Subacute Ruminal Acidosis

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