Vitamin D and Susceptibility of Chronic Lung Diseases: Role of Epigenetics

Sundar, Isaac K.; Rahman, Irfan

doi:10.3389/fphar.2011.00050

Cited by 74 publications

(48 citation statements)

References 123 publications

(181 reference statements)

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“…Oxidative stress and/or glutathione depletion is associated with increased histone acetylation (119,120). CS-mediated alterations in chromatin remodeling are shown to be involved in sustained lung inflammatory diseases, such as COPD (83,140,143,179,186). CBP and p300 are the known coactivators that possess intrinsic HAT activity.…”

Section: Histone Acetyltransferasesmentioning

confidence: 99%

Oxidative Stress and Chromatin Remodeling in Chronic Obstructive Pulmonary Disease and Smoking-Related Diseases

Sundar

Yao

Rahman

2013

Antioxidants & Redox Signaling

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162

107

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Significance: Chronic obstructive pulmonary disease (COPD) is predominantly a tobacco smoke-triggered disease with features of chronic low-grade systemic inflammation and aging (inflammaging) of the lung associated with steroid resistance induced by cigarette smoke (CS)-mediated oxidative stress. Oxidative stress induces various kinase signaling pathways leading to chromatin modifications (histone acetylation/deacetylation and histone methylation/demethylation) in inflammation, senescence, and steroid resistance. Recent Advances: Histone mono-, di-, or tri-methylation at lysine residues result in either gene activation (H3K4, H3K36, and H3K79) or repression (H3K9, H3K27, and H3K20). Cross-talk occurs between various epigenetic marks on histones and DNA methylation. Both CS and oxidants alter histone acetylation/deacetylation and methylation/ demethylation leading to enhanced proinflammatory gene expression. Chromatin modifications occur in lungs of patients with COPD. Histone deacetylase 2 (HDAC2) reduction (levels and activity) is associated with steroid resistance in response to oxidative stress. Critical Issues: Histone modifications are associated with DNA damage/repair and epigenomic instability as well as premature lung aging, which have implications in the pathogenesis of COPD. HDAC2/SIRTUIN1 (SIRT1)-dependent chromatin modifications are associated with DNA damage-induced inflammation and senescence in response to CS-mediated oxidative stress. Future Directions: Understanding CS/oxidative stress-mediated chromatin modifications and the cross-talk between histone acetylation and methylation will demonstrate the involvement of epigenetic regulation of chromatin remodeling in inflammaging. This will lead to identification of novel epigenetic-based therapies against COPD and other smoking-related lung diseases. Pharmacological activation of HDAC2/SIRT1 or reversal of their oxidative post-translational modifications may offer therapies for treatment of COPD and CS-related diseases based on epigenetic histone modifications.

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Section: Histone Acetyltransferasesmentioning

confidence: 99%

Oxidative Stress and Chromatin Remodeling in Chronic Obstructive Pulmonary Disease and Smoking-Related Diseases

Sundar

Yao

Rahman

2013

Antioxidants & Redox Signaling

Self Cite

162

107

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“…It is widely accepted that vitamin D is also involved in many chronic inflammatory diseases like chronic kidney disease, [29] chronic lung disease, [30] periodontitis, [31] and autoimmune rheumatic diseases, [32] mainly because of its effects on the immune response. Vitamin D activates monocytes, stimulates cell-mediated immunity, and suppresses lymphocyte proliferation.…”

Section: Introductionmentioning

confidence: 99%

C-Reactive Protein Levels and Vitamin D Receptor Polymorphisms as Markers in Predicting Cachectic Syndrome in Cancer Patients

et al. 2012

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Background and Objective: In patients with advanced cancer, cachexia correlates with low performance status and poor quality of life. In addition, cachexia may be associated with reduced response to chemoradiotherapy and a poor prognosis in cancer patients. Nearly all forms of cachexia are closely associated with chronic inflammation and elevated levels of inflammatory and pro-inflammatory circulating factors, including C-reactive protein (CRP), which is considered a valid laboratory and clinical marker. Among the different pathways involved in the production of inflammatory cytokines and chemokines, the vitamin Dvitamin D receptor (VDR) axis plays a fundamental role.In this study, we explore the possible association between CRP and key factors pertaining to the vitamin D axis -in particular, VDR gene polymorphisms -in cancer patients with cachexia. Although certain tumor types are more commonly associated with cachexia, even within the same tumor type there are significant differences in the extent and duration of cachexia. Such variations may be due to polymorphisms of the VDR gene that could lead to cachexia-prone genotypes or to cachexia-resistant genotypes. Identification of such genotypes could be very helpful in the management of cancer patients. Methods: Forty-three cancer patients were recruited by the Nutritional Unit of the Prato Hospital. Data on age, gender, type of cancer, stage of cancer, and nutritional assessment, as well as transferrin, ferritin, albumin, and CRP levels, were collected. Genomic DNA was extracted from peripheral blood leukocytes and amplified by polymerase chain reaction. BsmI, ApaI, TaqI, and FokI polymorphisms of the VDR gene were investigated using the respective restriction enzymes. For the different VDR polymorphisms, the absence or presence of the restriction sites were designated with capital or small letters, respectively. For example, for the BsmI polymorphism, the presence of the undigested fragment identified the B allele, whereas the presence of the digested fragment identified the b allele. Results: Cancer patients with cachexia have higher CRP levels compared with non-cachectic cancer patients, independently from the genotype. In cachectic patients, the presence of specific VDR BsmI and TaqI alleles was associated with higher CRP levels. In particular, the VDR b and T alleles were more frequent in cachectic cancer patients with elevated CRP levels than in cachectic patients with normal CRP levels. Conclusion: From these results, we hypothesize that there is an association between BsmI and TaqI VDR gene polymorphisms and the cachectic syndrome. In particular, we propose that in cancer patients, the concomitance of b and T alleles with elevated CRP levels may represent an early clinical predictor for the development of a more aggressive form of cachexia.

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“…Vitamin D deficiency may lead to increased inflammation, increased risk of viral infections, and the development of asthma (59)(60)(61)(62)(63).…”

Section: Influence Of Other Environmental Exposures On Infant Viral Imentioning

confidence: 99%

Toward Primary Prevention of Asthma. Reviewing the Evidence for Early-Life Respiratory Viral Infections as Modifiable Risk Factors to Prevent Childhood Asthma

Feldman

Moore

et al. 2015

Am J Respir Crit Care Med

173

172

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A first step in primary disease prevention is identifying common, modifiable risk factors that contribute to a significant proportion of disease development. Infant respiratory viral infection and childhood asthma are the most common acute and chronic diseases of childhood, respectively. Common clinical features and links between these diseases have long been recognized, with early-life respiratory syncytial virus (RSV) and rhinovirus (RV) lower respiratory tract infections (LRTIs) being strongly associated with increased asthma risk. However, there has long been debate over the role of these respiratory viruses in asthma inception. In this article, we systematically review the evidence linking early-life RSV and RV LRTIs with asthma inception and whether they could therefore be targets for primary prevention efforts.

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Vitamin D and Susceptibility of Chronic Lung Diseases: Role of Epigenetics

Cited by 74 publications

References 123 publications

Oxidative Stress and Chromatin Remodeling in Chronic Obstructive Pulmonary Disease and Smoking-Related Diseases

Oxidative Stress and Chromatin Remodeling in Chronic Obstructive Pulmonary Disease and Smoking-Related Diseases

C-Reactive Protein Levels and Vitamin D Receptor Polymorphisms as Markers in Predicting Cachectic Syndrome in Cancer Patients

Toward Primary Prevention of Asthma. Reviewing the Evidence for Early-Life Respiratory Viral Infections as Modifiable Risk Factors to Prevent Childhood Asthma

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