Aldosterone Synthesis and Cytokine Production in Human Peripheral Blood Mononuclear Cells

Miura, Rika; Nakamura, Kazufumi; Miura, Daiji; Miura, Aya; Hisamatsu, Ken-ichi; Kajiya, Masahito; Hashimoto, Katsushi; Nagase, Satoshi; Morita, Hiroshi; Kusano, Kengo; Emori, Tetsuro; Ishihara, Kazuhíko; Ohe, Tohru

doi:10.1254/jphs.fp0060801

Cited by 23 publications

(21 citation statements)

References 54 publications

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“…Epoxide hydrolase (EH), GST, N-acetyltransferase, and ST also have been described (Raucy et al, 1997;Baron et al, 1998;Dassi et al, 1998;Spencer et al, 1999;Stärkel et al, 1999;Takeda et al, 1999;Boucher et al, 2000;Krovat et al, 2000;Nakamoto et al, 2000;Nguyen et al, 2000;Smart and Daly, 2000;Finnström et al, 2001Finnström et al, , 2002Hannon-Fletcher et al, 2001;Asghar et al, 2002;Carcillo et al, 2003;Gashaw et al, 2003;Landi et al, 2003Landi et al, , 2005Lin et al, 2003;Toide et al, 2003;Tuominen et al, 2003;Furukawa et al, 2004;Lampe et al, 2004;Yamamoto et al, 2004;Haas et al, 2005;Liangpunsakul et al, 2005;Miura et al, 2006). However, study of the expression of both DME and TF is rarely conducted at the same time.…”

mentioning

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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mentioning

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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“…The collected cells were washed 3 times with phosphate-buffered saline (PBS), resuspended in the conditioned medium, and incubated at 37°C under a humidified atmosphere with 5% CO 2 . 27,28) Medium and Reagents The conditioned medium was RPMI 1640 (Sigma, Montana, U.S.A.) supplemented with 10% heat-inactivated fetal bovine serum (Sigma, Montana, U.S.A.), 50 mM 2-mercaptoethanol, and 100 mg/ml kanamycin. 27,28) Fura-2 acetoxymethyl ester (fura-2/AM, a [Ca 2ϩ ] i indicator) 1 mM solution in dry dimethyl sulfoxide was purchased from Invitrogen (California, U.S.A.).…”

Section: Isolation Of Pbmcsmentioning

confidence: 99%

“…27,28) Medium and Reagents The conditioned medium was RPMI 1640 (Sigma, Montana, U.S.A.) supplemented with 10% heat-inactivated fetal bovine serum (Sigma, Montana, U.S.A.), 50 mM 2-mercaptoethanol, and 100 mg/ml kanamycin. 27,28) Fura-2 acetoxymethyl ester (fura-2/AM, a [Ca 2ϩ ] i indicator) 1 mM solution in dry dimethyl sulfoxide was purchased from Invitrogen (California, U.S.A.). 29) PHA was purchased from Wako Pure Chemical Industries (Osaka, Japan).…”

Section: Isolation Of Pbmcsmentioning

confidence: 99%

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Cytokine Reducing Effect of Azelnidipine in Human Peripheral Blood Mononuclear Cells

Miura

Nakamura

Miura

et al. 2010

Biological & Pharmaceutical Bulletin

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“…Experiments that have been published to date exploring AT 1 R expression have used cell populations with limited purity and with little characterization of the effect of AngII on monocytes in vitro. 4,5,15,[23][24][25][26] The purpose of this study was to evaluate the direct effect of AngII on purified CD14 + /CD16 -monocyte isolates in vitro in an effort to better understand mechanisms by which AngII can modulate the migration of monocytes to the myocardium. We propose that studying a purified monocyte population, a method not used to date by other investigators, will provide an accurate portrayal of the direct effects of AngII on monocytes in terms of cytokine production and cell surface expression of AT 1 R.…”

Section: Introductionmentioning

confidence: 99%

Highly purified human peripheral blood monocytes produce IL-6 but not TNFα in response to angiotensin II

Gelinas

Falkenham

Oxner

et al. 2011

J Renin Angiotensin Aldosterone Syst

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Hypothesis: Monocytes produce pro-inflammatory cytokines in response to Angiotensin II (AngII). Introduction: AngII has been suggested by many to be pro-inflammatory and likely to contribute to the migration of leukocytes in patients with cardiovascular conditions. Materials and methods: Monocytes were purified from peripheral blood mononuclear cells (PBMCs) by negative selection using antibodies conjugated to magnetic beads. Detection of CD14 + and AT 1 R expression was achieved by double-labeling flow cytometry. Highly purified monocytes were then stimulated with AngII (6 and 24 h) to assess IL-6 and TNF-a transcript levels by qRT-PCR and protein secretion by ELISA. Results: Monocytes comprised 9.7 ± 2.0% of the PBMCs. Monocyte isolation by negative selection yielded a purity of up to 99.8%. We demonstrated AT 1 R expression on 9.5 ± 0.3% of highly purifed CD14 + /CD16 -monocytes. Stimulation of highly purified monocytes with AngII resulted in increased transcript levels of IL-6 at 6 h but not at 24 h, and increased secretion of IL-6 in a dose-dependent manner compared with controls (p <0.01). Conversely, there was no increase in TNF-a mRNA transcripts or protein secretion. Conclusions: We provide evidence that a CD14 + /CD16 -subset of highly purified human monocytes express AT 1 R and respond to AngII exposure in vitro by producing IL-6 but not TNF-a.

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Aldosterone Synthesis and Cytokine Production in Human Peripheral Blood Mononuclear Cells

Cited by 23 publications

References 54 publications

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

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

Cytokine Reducing Effect of Azelnidipine in Human Peripheral Blood Mononuclear Cells

Highly purified human peripheral blood monocytes produce IL-6 but not TNFα in response to angiotensin II

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