Systemic and pulmonary effects of fluticasone administered through a metered-dose inhaler in rats

Sorkness, Ronald L.; Remus, J.L.; Rosenthal, Louis A.

doi:10.1016/j.jaci.2004.07.015

Cited by 18 publications

(14 citation statements)

References 17 publications

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“…Thus we elected to use pharmacologic approaches to block Pin1 in a well-established Brown Norway rat model of allergic airway inflammation. 20 However, before juglone use in vivo, thymocytes from Pin1 WT and knockout mice were activated in vitro with anti-CD3/anti-CD28 with or without juglone for 3 hours (Fig 1). GM-CSF mRNA expression was dramatically increased (approximately 55-fold) in activated WT thymocytes, which was reduced by approximately 80% by juglone.…”

Section: Resultsmentioning

confidence: 99%

“…19 Allergen sensitization and challenges Brown Norway rats (BN/SsNHsd substrain; Harlan, Indianapolis, Ind) 10 to 13 weeks of age were sensitized and challenged with short ragweed pollen extract, as previously described. 20 Briefly, rats were sensitized by means of subcutaneous injection, followed 2 weeks later by aerosol challenge (2% for 20 minutes). On the day before, the day of, and the day after the aerosol challenge, rats received an intraperitoneal injection of juglone (1 mg/kg body weight per day) or vehicle.…”

Section: Pin1 2/2 Micementioning

confidence: 99%

“…On the day before, the day of, and the day after the aerosol challenge, rats received an intraperitoneal injection of juglone (1 mg/kg body weight per day) or vehicle. 19 Two days after the aerosol challenge, at the peak of eosinophilic inflammation, 20 BAL of the right lungs, processing of the BAL fluid cells, and formalin fixation of the left lungs were performed as described previously. 20 All animal procedures conformed to the ''Guide for the care and use of laboratory animals'' and were approved by the University of Wisconsin Animal Care and Use Committee.…”

Section: Pin1 2/2 Micementioning

confidence: 99%

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A critical role for Pin1 in allergic pulmonary eosinophilia in rats

Esnault

Rosenthal²,

Sedgwick³

et al. 2007

Journal of Allergy and Clinical Immunology

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Section: Resultsmentioning

confidence: 99%

Section: Pin1 2/2 Micementioning

confidence: 99%

Section: Pin1 2/2 Micementioning

confidence: 99%

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A critical role for Pin1 in allergic pulmonary eosinophilia in rats

Esnault

Rosenthal²,

Sedgwick³

et al. 2007

Journal of Allergy and Clinical Immunology

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“…Peripheral blood was obtained by venipuncture from normal or mildly atopic donors. Peripheral blood or BAL fluid Eos were purified with a negative immunomagnetic procedure as described previously (56). Cells were used only when they were more than 99% pure.…”

Section: Figurementioning

confidence: 99%

Pin1 regulates TGF-β1 production by activated human and murine eosinophils and contributes to allergic lung fibrosis

Shen¹,

et al. 2008

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Eosinophilic inflammation is a cornerstone of chronic asthma that often culminates in subepithelial fibrosis with variable airway obstruction. Pulmonary eosinophils (Eos) are a predominant source of TGF-β1, which drives fibroblast proliferation and extracellular matrix deposition. We investigated the regulation of TGF-β1 and show here that the peptidyl-prolyl isomerase (PPIase) Pin1 promoted the stability of TGF-β1 mRNA in human Eos. In addition, Pin1 regulated cytokine production by both in vitro and in vivo activated human Eos. We found that Pin1 interacted with both PKC-α and protein phosphatase 2A, which together control Pin1 isomerase activity. Pharmacologic blockade of Pin1 in a rat asthma model selectively reduced eosinophilic pulmonary inflammation, TGF-β1 and collagen expression, and airway remodeling. Furthermore, chronically challenged Pin1 -/-mice showed reduced peribronchiolar collagen deposition compared with wild-type controls. These data suggest that pharmacologic suppression of Pin1 may be a novel therapeutic option to prevent airway fibrosis in individuals with chronic asthma.

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“…Pulmonary inflammation and remodeling were assessed by obtaining cells from the air space via bronchoalveolar lavage (BAL) of the right lung and by quantitative histology from paraffin sections of the left lung (48). The total BAL leukocyte count was determined with a cell counter (Beckman Coulter, Hialeah, FL), and the differential cell count was obtained from 200 cells on a cytospin slide stained with eosinmethylene blue stain.…”

Section: Methodsmentioning

confidence: 99%

Altered allergen-induced eosinophil trafficking and physiological dysfunction in airways with preexisting virus-induced injury

Sorkness

Herricks²,

Szakaly³

et al. 2007

American Journal of Physiology-Lung Cellular and Molecular Phys

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August 11, 2006; doi:10.1152/ajplung.00234.2006.-Although both asthmatics and allergic rhinitics develop an acute inflammatory response to lower airway allergen challenge, only asthmatics experience airway obstruction resulting from chronic environmental allergen exposure. Hypothesizing that asthmatic airways have an altered response to chronic allergic inflammation, we compared the effects of repeated low-level exposures to inhaled Alternaria extract in sensitized rats with preexisting chronic postbronchiolitis airway dysfunction versus sensitized controls with normal airways. Measurements of air space (bronchoalveolar lavage) inflammatory cells, airway goblet cells, airway wall collagen, airway wall eosinophils, airway alveolar attachments, and pulmonary physiology were conducted after six weekly exposures to aerosolized saline or Alternaria extract. Postbronchiolitis rats, but not those starting with normal airways, had persistent increases in airway wall eosinophils, goblet cell hyperplasia in small airways, and loss of lung elastic recoil after repeated exposure to aerosolized Alternaria extract. Despite having elevated airway wall eosinophils, the postbronchiolitis rats had no eosinophils in bronchoalveolar lavage at 5 days after the last allergen exposure, suggesting altered egression of tissue eosinophils into the air space. In conclusion, rats with preexisting airway pathology had altered eosinophil trafficking and allergen-induced changes in airway epithelium and lung mechanics that were absent in sensitized control rats that had normal airways before the allergen exposures. postbronchiolitis sequelae; lung elastic recoil; rats; Alternaria MOST PERSONS WITH ASTHMA have allergies, and there are strong epidemiologic associations between exposure to allergens and both the inception and the aggravation of asthma (15,31,36). Direct evidence for links between allergens and asthma include worsening of asthma during 4 wk of dust mite exposure mimicking the level found in bedrooms (1) and improvement of asthma during allergen avoidance (44). However, not all atopic persons who are exposed to allergens have an asthmatic phenotype, even though pulmonary allergen challenge in nonasthmatic allergic subjects elicits an acute eosinophilic inflammatory response that resembles that of asthmatic subjects (5,22,43). One possible mechanism explaining this may be that a persistent asthma phenotype develops as a consequence of usual environmental inflammatory stimuli interacting with airways made vulnerable by an initial inflammatory event occurring during a period of maturation of both the lung structure and the immune system (19).We therefore hypothesized that asthmatic airways are more vulnerable than normal airways to chronic low-level allergen exposure, resulting in a more persistent inflammatory milieu that contributes to airway dysfunction. To address this hypothesis, we used the rat model of postbronchiolitis chronic airway dysfunction (39). In this model, rats are infected with parainfluenza virus early in life, a...

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Systemic and pulmonary effects of fluticasone administered through a metered-dose inhaler in rats

Cited by 18 publications

References 17 publications

A critical role for Pin1 in allergic pulmonary eosinophilia in rats

A critical role for Pin1 in allergic pulmonary eosinophilia in rats

Pin1 regulates TGF-β1 production by activated human and murine eosinophils and contributes to allergic lung fibrosis

Altered allergen-induced eosinophil trafficking and physiological dysfunction in airways with preexisting virus-induced injury

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