Expression of nuclear retinoic acid receptor in peripheral blood mononuclear cells (PBMC) of healthy subjects

Szabová, Ľudmila; Macejova, Dana; Dvorcakova, M; Mostböck, Sven; Blazícková, S; Zórad, Štefan; Walrand, Stéphane; Cardinault, Nicolas; Vasson, M.-P.; Rock, Erin M.; Brtko, Július

doi:10.1016/s0024-3205(02)02307-x

Cited by 23 publications

(16 citation statements)

References 16 publications

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“…No RXR mRNA was detected in the PBMC of either group. Previously published data are controversial with similar findings to ours (our data were consistent with the observation of Lomo et al (1998) while Szabova et al (2003) showed the contrary, that is, the expression of RXR mRNA in human PBMC). Hypothyroidism did not induce any modifications of RXR expression.…”

Section: Discussionsupporting

confidence: 93%

“…The RA nuclear receptors RAR , RAR , RXR and RXR have also been found in these cells (Szabova et al 2003). Given that retinoids and thyroid hormones have mainly intracellular action, the aim of the present study was twofold: firstly, to establish the effect of primary hypothyroidism on the expression of TR and TR in human PBMC; secondly, to clarify the effect on the expression of the retinoid nuclear receptors RAR , RAR and RXR in PBMC.…”

Section: Introductionmentioning

confidence: 93%

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Decreased expression of retinoid nuclear receptor (RARα and RARγ) mRNA determined by real-time quantitative RT-PCR in peripheral blood mononuclear cells of hypothyroid patients

Féart¹,

Vallortigara²,

Higueret³

et al. 2005

Journal of Molecular Endocrinology

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In vivo assessment of the cellular impact of thyroid hormones on target tissues might be of help for physiological studies and to evaluate the consequences of various diseases of the thyroid gland in humans. Given the tenuous relationship between retinoid and tri-iodothyronine (T 3 ) status and that retinoids have also intracellular roles, the aim of this study was to determine the effect of hypothyroidism on the expression of T 3 nuclear receptors (TR) and retinoic acid nuclear receptors (RAR, RXR) in human peripheral blood mononuclear cells (PBMC). Using real time RT-PCR, we quantified the relative amount of mRNA of the thyroid (TR and TR ) and retinoid (RAR , RAR , and RXR ) nuclear receptors in PBMC of euthyroid (n=22) compared with hypothyroid (n=22) subjects. Classical plasma parameters (free T 3 (FT 3 ), free thyroxine (T 4 ) (FT 4 ), thyroid-stimulating hormone (TSH), retinol (ROH), retinol-binding protein (RBP) and transthyretin (TTR)) were also measured. In hypothyroid subjects, the concentration of TSH was elevated, and dramatically low T 3 and T 4 concentrations were associated with a decrease in the expression of TR . Expression of RAR and RAR significantly decreased in hypothyroid versus control subjects, while an increased concentration of ROH was emphasised by hypothyroidism. These results first indicated that primary hypothyroidism induces hypoactivation of the retinoid nuclear pathway in PBMC, which was not predicted by the plasma ROH level. Further investigations will be necessary to evaluate these parameters in very small changes in thyroid hormone production such as mild (subclinical) hypothyroidism.

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Section: Discussionsupporting

confidence: 93%

Section: Introductionmentioning

confidence: 93%

Decreased expression of retinoid nuclear receptor (RARα and RARγ) mRNA determined by real-time quantitative RT-PCR in peripheral blood mononuclear cells of hypothyroid patients

Féart¹,

Vallortigara²,

Higueret³

et al. 2005

Journal of Molecular Endocrinology

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“…Expression of retinoic acid receptor and retinoid X receptor (RXR) has been described in healthy subject PBMC but only qualitatively (Szabova et al, 2003). No one has looked in healthy lymphocytes for the three other transcriptional activation mechanisms involved in P450 regulation: CAR-RXR, PXR-RXR, and PPAR␣-RXR.…”

Section: Downloaded Frommentioning

confidence: 99%

Transcription Factor and Drug-Metabolizing Enzyme Gene Expression in Lymphocytes from Healthy Human Subjects

Siest

Jeannesson²,

Marteau³

et al. 2007

Drug Metab Dispos

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ABSTRACT:We aimed to measure simultaneously the expression of drugmetabolizing enzymes (DME) and transcription factors (TF) with high importance in cardiovascular physiopathology in lymphocytes from healthy subjects. RNA was isolated from peripheral blood mononuclear cells (PBMC) of 20 subjects from the Stanislas Cohort. We used a microarray approach to measure 16 DME and 13 TF. Cytochromes P450 (P450s), including CYP2C19, CYP2C9, CYP2J2, CYP2D6, CYP1A1, CYP4F2, CYP4A11, CYP2E1, CYP11B2, CYP2C18, and CYP2A6, were expressed in all the subjects. CYP3A4 and CYP3A5 were not expressed. Glutathione S-transferases (GST) were expressed, but GSTM1 was seen only in some subjects. Pregnane X receptor (PXR), myocyte enhancer factor 2, vitamin D receptor, liver X receptor (LXR)-␣, aryl hydrocarbon receptor (AHR), T-cell factor 7, constitutive androstane receptor, and aryl hydrocarbon receptor nuclear translocator (ARNT) were expressed in the majority of the subjects. Glucocorticoid receptor, peroxisome proliferator-activated receptor (PPAR)-␥, and LXR␤ were expressed only in some individuals. PPAR␣ mRNA was found in one subject only, and farnesoid X-activated receptor was not expressed. In addition, we found significant correlations between the expression of AHR, ARNT, and CYP1A1 and between PXR and P450 involved in leukotriene metabolism (CYP2C, CYP4F2, CYP4A11, CYP2J2, and CYP11B2). We describe here for the first time the presence of the majority of TF and DME in PBMC of healthy subjects without previous induction. The expression of these genes in lymphocytes could be a useful tool for further studying the physiological and pathological variations of DME and TF related to environment, to drug intake, and to cardiovascular metabolic cycles.Drug-metabolizing enzymes (DME) and cytochromes P450 (P450s) in particular are central players in cardiovascular health and disease (Elbekai and El-Kadi, 2006). DME are important in the follow-up of cardiovascular drugs because many drugs are metabolized by them. These enzymes are also involved in the metabolism of natural substrates (such as leukotrienes, steroids, and bile acids) that are in turn implicated in several cardiovascular-related pathways, including inflammation, lipid metabolism, and blood pressure regulation. In addition, many environmental factors (tobacco, polycyclic hydrocarbons and dioxins, alcohol, and nutrients) modulate their patterns of expression, and expression of several of these genes is under control of transcription factors (TF), such as the pregnane X receptor (PXR), the constitutive androstane receptor (CAR), the glucocorticoid receptor (GR), or the aryl hydrocarbon receptor (AHR).Finally, some polymorphisms in genes coding for these DME are well known to influence the level of expression with clinical and pharmacological relevance.Some DME, including glutathione S-transferases (GST), N-acetyltransferases, and sulfotransferases (ST), are soluble enzymes measurable as phenotypes in the plasma. However, the majority is mainly localized in the endoplasmic retic...

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“…The Journal of Immunology, 2016, 197: 244-255. P regnane X receptor (PXR) is an adopted orphan nuclear receptor (NR) predominantly expressed in the liver and intestine, and it also finds expression in immune cells such as lymphocytes, monocytes, and macrophages (1,2). PXR modulates a wide array of physiological functions such as energy homeostasis, apoptosis, and inflammation (3,4).…”

mentioning

confidence: 99%

Human Xenobiotic Nuclear Receptor PXR AugmentsMycobacterium tuberculosisSurvival

Bhagyaraj

Nanduri

Saini

et al. 2016

The Journal of Immunology

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Mycobacterium tuberculosis can evade host defense processes, thereby ensuring its survival and pathogenesis. In this study, we investigated the role of nuclear receptor, pregnane X receptor (PXR), in M. tuberculosis infection in human monocyte–derived macrophages. In this study, we demonstrate that PXR augments M. tuberculosis survival inside the host macrophages by promoting the foamy macrophage formation and abrogating phagolysosomal fusion, inflammation, and apoptosis. Additionally, M. tuberculosis cell wall lipids, particularly mycolic acids, crosstalk with human PXR (hPXR) by interacting with its promiscuous ligand binding domain. To confirm our in vitro findings and to avoid the reported species barrier in PXR function, we adopted an in vivo mouse model expressing hPXR, wherein expression of hPXR in mice promotes M. tuberculosis survival. Therefore, pharmacological intervention and designing antagonists to hPXR may prove to be a promising adjunct therapy for tuberculosis.

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Expression of nuclear retinoic acid receptor in peripheral blood mononuclear cells (PBMC) of healthy subjects

Cited by 23 publications

References 16 publications

Decreased expression of retinoid nuclear receptor (RARα and RARγ) mRNA determined by real-time quantitative RT-PCR in peripheral blood mononuclear cells of hypothyroid patients

Decreased expression of retinoid nuclear receptor (RARα and RARγ) mRNA determined by real-time quantitative RT-PCR in peripheral blood mononuclear cells of hypothyroid patients

Transcription Factor and Drug-Metabolizing Enzyme Gene Expression in Lymphocytes from Healthy Human Subjects

Human Xenobiotic Nuclear Receptor PXR AugmentsMycobacterium tuberculosisSurvival

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