Theophylline and Dexamethasone Induce Peroxisome Proliferator-Activated Receptor-γ Expression in Human Eosinophils

Usami, Atsuko; Ueki, Shigeharu; Ito, Wataru; Kobayashi, Yoshiki; Chiba, Takahito; Mahemuti, Gulixian; Oyamada, Hirokazu; Kamada, Yumiko; Fujita, Mutsuhiro; Kato, Hikari; Saito, Norihiro; Kayaba, Hiroyuki; Chihara, Junichi

doi:10.1159/000092376

Cited by 15 publications

(12 citation statements)

References 41 publications

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“…We first studied the effect of 17β-estradiol on PPARγ protein levels using a flow cytometer. In line with our previous report, purified fresh eosinophils constitutively expressed PPARγ [5, 16, 17]. Eosinophils were cultured with various concentrations of 17β-estradiol for 24 h, followed by measurement of PPARγ expression (fig.…”

Section: Resultssupporting

confidence: 56%

“…Although the influence of estradiol on cell function was previously assigned exclusively to genomic reaction, it is known that estradiol activates the membrane form of ER and can rapidly induce intracellular cyclic AMP (cAMP) elevation [24]. Recently, we found that the bronchodilators theophylline and procaterol upregulated PPARγ mRNA and protein expression in eosinophils [15, 16]. Because the functions of these drugs are mediated through cAMP signaling, elevated cAMP in eosinophils might play a role in augmentation of PPARγ expression.…”

Section: Discussionmentioning

confidence: 99%

“…Flow cytometry was used for studying the protein expression of PPARγ as previously described [15, 16]. Purified eosinophils were washed twice with PBS and then permeabilized with FIX & PERM (Caltag Lab., San Francisco, Calif., USA).…”

Section: Methodsmentioning

confidence: 99%

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Regulation of Peroxisome Proliferator-Activated Receptor-γ Expression in Human Eosinophils by Estradiol

Ueki

Oguma²,

Usami³

et al. 2009

Int Arch Allergy Immunol

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Background: Peroxisome proliferator-activated receptor-γ (PPARγ) is a nuclear receptor that regulates not only adipogenesis but also immune reaction. We previously demonstrated that human eosinophils expressed functional PPARγ, although the modulator of PPARγ expression is less well understood. Because clinical studies have shown that the efficacy of PPARγ agonists as insulin sensitizers is stronger in women than in men, we investigated whether sex hormones caused any changes in eosinophil PPARγ expression levels. Methods: First, purified human peripheral blood eosinophils were cultured with 17β-estradiol for 24 h, followed by PPARγ measurement using a flow cytometer. Next, eosinophil PPARγ expression and serum estradiol were studied in 10 healthy women during the menstrual and follicular phases to identify the physiological significance of estradiol. Eosinophil PPARγ expression was also compared in 22 men, 21 non-pregnant women, and 15 pregnant women. Results: We observed that PPARγ protein expression in eosinophils was significantly enhanced by 10^–6M 17β-estradiol. Although serum estradiol concentration was increased during the follicular phase, PPARγ expression levels were not affected by the menstrual cycle. In addition, no significant differences in PPARγ expression were observed in terms of sex and pregnancy. Conclusions: These findings suggest that estradiol potentially upregulates eosinophil PPARγ expression in vitro, although some other mechanisms might be involved in its regulation in vivo.

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Section: Resultssupporting

confidence: 56%

Section: Discussionmentioning

confidence: 99%

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Regulation of Peroxisome Proliferator-Activated Receptor-γ Expression in Human Eosinophils by Estradiol

Ueki

Oguma²,

Usami³

et al. 2009

Int Arch Allergy Immunol

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“…Thus, it has been postulated that the anti-inflammatory effects may be due to mechanisms other than phosphodiesterase inhibition. Adenosine receptor antagonism (27), an increase in histone deacetylase activity (28), and/or enhanced messenger RNA and protein levels of peroxisomal proliferator-activated receptor-gamma (PPAR-gamma) expression (29) have all been reported as potential explanations.…”

Section: Discussionmentioning

confidence: 99%

A Prospective Assessment of the Effect of Aminophylline Therapy on Urine Output and Inflammation in Critically Ill Children

et al. 2014

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Background: Aminophylline, an established bronchodilator, is also purported to be an effective diuretic and anti-inflammatory agent. However, the data to support these contentions are scant. We conducted a prospective, open-label, single arm, single center study to assess the hypothesis that aminophylline increases urine output and decreases inflammation in critically ill children.Methods: Children less than 18 years of age admitted to the pediatric intensive care unit who were prescribed aminophylline over a 24-h period were eligible for study. The use and dosing of aminophylline was independent of the study and was at the discretion of the clinical team. Data analyzed consisted of demographics, diagnoses, medications, and markers of pulmonary function, renal function, and inflammation. Data were collected at baseline and at 24-h after aminophylline initiation with primary outcomes of change in urine output and inflammatory cytokine concentrations.Results: Thirty-five patients were studied. Urine output increased significantly with aminophylline use [median increase 0.5 mL/kg/h (IQR: −0.3, 1.3), p = 0.05] while blood urea nitrogen and creatinine concentrations remained unchanged. Among patients with elevated C-reactive protein concentrations, levels of both interleukin-6 (IL-6) and IL-10 decreased at 24 h of aminophylline therapy. There were no significant differences in pulmonary compliance or resistance among patients invasively ventilated at both time points. Side effects of aminophylline were detected in 7 of 35 patients.Conclusion: Although no definitive conclusions can be drawn from this study, aminophylline may be a useful diuretic and effective anti-inflammatory medication in critically ill children. Given the incidence of side effects, the small sample size and the uncontrolled study design, further study is needed to inform the appropriate use of aminophylline in these children.

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“…However, the PPARγ expression in eosinophils was unaltered on stimulation with IL-5, which is a major eosinophil-activating cytokine that is produced abundantly at allergic inflammatory sites [26]; further, it showed no correlation with the activation marker CD25 or eosinophilic cationic proteins in serum [32]. Recent studies in our laboratory indicated that de novo synthesis of PPARγ was induced in human eosinophils by culturing them along with drugs such as β-adrenoceptor agonist or theophylline at therapeutic concentrations [26, 33]. Therefore, an alternative explanation is that these drugs might augment PPARγ expression in asthmatic subjects.…”

Section: Eosinophils Express Pparγ: An Intracellular Target Of 15d-pgj2mentioning

confidence: 99%

Anti- and Proinflammatory Effects of 15-Deoxy-Δ12,14-Prostaglandin J2(15d-PGJ2) on Human Eosinophil Functions

Ueki

Kato

Kobayashi

et al. 2007

Int Arch Allergy Immunol

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The cyclopentenone prostaglandin 15-deoxy-Δ^12,14-prostaglandin J₂ (15d-PGJ₂) is recognized as a potent lipid mediator that is derived from PGD₂, which is produced abundantly in allergic inflammatory sites. It is now established that 15d-PGJ₂ negatively regulates cellular functions through its intracellular targets such as peroxisome proliferator-activated receptor-γ (PPARγ). However, recent studies revealed that 15d-PGJ₂ appears to possess not only anti-inflammatory activities but also a proinflammatory potential depending on its concentration and the activation state of the target cell. For instance, at low concentrations, 15d-PGJ₂ enhances eotaxin-induced chemotaxis, shape change, and actin reorganization in eosinophils through its ligation with PPARγ. Moreover, 15d-PGJ₂ itself is a potent chemoattractant, and it induces calcium mobilization, and up-regulates CD11b expression through its membrane receptor – chemoattractant receptor-homologous molecule expressed on Th2 cells (CRTH2). Conversely, at high concentrations, 15d-PGJ₂ inhibits eosinophil survival by inducing apoptosis in a PPARγ-independent manner. Here, we discuss the pathophysiological roles of 15d-PGJ₂ that could act as a paracrine, autocrine, and intracrine substance to regulate eosinophil functions.

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Theophylline and Dexamethasone Induce Peroxisome Proliferator-Activated Receptor-γ Expression in Human Eosinophils

Cited by 15 publications

References 41 publications

Regulation of Peroxisome Proliferator-Activated Receptor-γ Expression in Human Eosinophils by Estradiol

Regulation of Peroxisome Proliferator-Activated Receptor-γ Expression in Human Eosinophils by Estradiol

A Prospective Assessment of the Effect of Aminophylline Therapy on Urine Output and Inflammation in Critically Ill Children

Anti- and Proinflammatory Effects of 15-Deoxy-Δ<sup>12,14</sup>-Prostaglandin J<sub>2</sub>(15d-PGJ<sub>2</sub>) on Human Eosinophil Functions

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