Suppression of allergen-induced airway inflammation and immune response by the peroxisome proliferator-activated receptor-alpha agonist fenofibrate

Delayre-Orthez, Carine; Becker, Julien; Auwerx, Johan; Frossard, Nelly; Pons, Ferrán

doi:10.1016/j.ejphar.2007.11.040

Cited by 33 publications

(31 citation statements)

References 23 publications

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“…Using PPAR-a -/-mice, the protective effects of WY on cytokines, eicosanoids, leukocyte infiltration and vascular leakage in models of ALI were abolished. These findings are in line with previous studies using WY or fenofibrate [31][32][33][34]. TRIFILIEFF et al [39] were unable to detect the same protective effects of the PPAR-a agonist GW 9578 in mice.…”

Section: Discussionsupporting

confidence: 80%

“…In contrast, treatment with fenofibrate reduced all examined parameters [33]. In line with these findings, allergic airway inflammation was reduced by fenofibrate in ovalbuminsensitised mice [34]. It has been demonstrated that activation of PPAR-a interferes with the expression of pro-inflammatory genes such as vascular cell adhesion molecule (VCAM)-1, PAF receptor and COX-2 [21,22].…”

Section: Discussionsupporting

confidence: 67%

“…Conversely, genetic deletion of PPAR-a induced prolonged and increased inflammation, as judged, for example, by increased generation of proinflammatory cytokines, leukocyte infiltration and mortality [31][32][33][34]. Whereas the data from the present ALI model are consistent with the first part of these findings, only a small (not significant) increase in the LPS-induced response was found in mice lacking functional PPAR-a and thus lacking responses from exogenous or endogenous activators.…”

Section: Discussioncontrasting

confidence: 34%

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Peroxisome proliferator-activated receptor-α reduces inflammation and vascular leakage in a murine model of acute lung injury

Schaefer¹,

Pose²,

Ott³

et al. 2008

Eur Respir J

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Acute lung injury (ALI) still represents a major cause of morbidity and mortality in intensive care units. Beneficial effects have been described after activation of the peroxisome proliferator-activated receptor (PPAR)-a by fibrates such as WY 14,643 (WY) in inflammatory models. In the present study, the impact of WY was investigated in a model of endotoxin (lipopolysaccharide; LPS)-induced ALI in mice.Intratracheal LPS challenge dose-dependently resulted in leukocyte invasion, protein leakage and release of tumour necrosis factor-a as well as macrophage inflammatory protein-2, prostaglandin E 2 and thromboxane B 2 into the alveolar space after 8 and 24 h. Lung ventilator compliance was reduced at both time-points. In isolated perfused mouse lungs, platelet-activating factor (PAF) induced an acute increase in pulmonary artery pressure (Ppa) and in capillary filtration coefficient (Kfc). WY significantly improved all features of ALI in vivo and blunted the increase in Kfc in isolated perfused mice lungs. In mice with genetic deletion of PPAR-a, all characteristics of ALI, Ppa, and Kfc were not significantly different from wild-type mice but WY failed to improve ALI and PAF-induced increase in Kfc.Activation of peroxisome proliferator-activated receptor-a by WY 14,643 reduced acute lung injury and vascular leakage. Fibrates may possess beneficial effects in acute pulmonary diseases beyond their lipid-lowering capability.

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Section: Discussionsupporting

confidence: 80%

Section: Discussionsupporting

confidence: 67%

Section: Discussioncontrasting

confidence: 34%

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Peroxisome proliferator-activated receptor-α reduces inflammation and vascular leakage in a murine model of acute lung injury

Schaefer¹,

Pose²,

Ott³

et al. 2008

Eur Respir J

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“…Serum OVAspecific IgG1, IgG2a, and IgE were determined by ELISA, as previously described (16). For the OVA recall assay, mediastinal lymph nodes (MLNs) were homogenized, and cells were plated at a density of 200,000 cells/well.…”

Section: Elisamentioning

confidence: 99%

“…Determination of total and differential cell counts in bronchoalveolar lavage fluids Bronchoalveolar lavage (BAL; 24 h after the last OVA challenge) was performed as described previously (16,17 …”

mentioning

confidence: 99%

A Dissociated Glucocorticoid Receptor Modulator Reduces Airway Hyperresponsiveness and Inflammation in a Mouse Model of Asthma

Reber

Daubeuf

Plantinga

et al. 2012

The Journal of Immunology

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The glucocorticoid receptor (GR) is a transcription factor able to support either target gene activation via direct binding to DNA or gene repression via interfering with the activity of various proinflammatory transcription factors. An improved therapeutic profile for combating chronic inflammatory diseases has been reported through selectively modulating the GR by only triggering its transrepression function. We have studied in this paper the activity of Compound A (CpdA), a dissociated GR modulator favoring GR monomer formation, in a predominantly Th2-driven asthma model. CpdA acted similarly to the glucocorticoid dexamethasone (DEX) in counteracting OVA-induced airway hyperresponsiveness, recruitment of eosinophils, dendritic cells, neutrophils, B and T cells, and macrophages in bronchoalveolar lavage fluid, lung Th2, Tc2, Th17, Tc17, and mast cell infiltration, collagen deposition, and goblet cell metaplasia. Both CpdA and DEX inhibited Th2 cytokine production in bronchoalveolar lavage as well as nuclear translocation of NF-κB and its subsequent recruitment onto the IκBα promoter in the lung. By contrast, DEX but not CpdA induces expression of the GR-dependent model gene MAPK phosphatase 1 in the lung, confirming the dissociative action of CpdA. Mechanistically, we demonstrate that CpdA inhibited IL-4–induced STAT6 translocation and that GR is essential for CpdA to mediate chemokine repression. In conclusion, we clearly show in this study the anti-inflammatory effect of CpdA in a Th2-driven asthma model in the absence of transactivation, suggesting a potential therapeutic benefit of this strategy.

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Performing Bronchoalveolar Lavage in the Mouse

Daubeuf

Frossard

2012

CP Mouse Biology

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Bronchoalveolar lavage (BAL) is a simple technique commonly used in humans to sample the contents of the epithelial lining fluid and determine the cellular and molecular composition of the pulmonary airways. In murine models, BAL makes it possible to sample immunological and inflammatory cell populations; it is indispensable for studying cell influx in disease models of the airways such as asthma and COPD. Cell counts can be combined with methods such as ELISA, immunoblot, immunohistochemistry, quantitative polymerase chain reaction, and HPLC to assess such inflammatory components as cytokines, growth factors, analytes, and receptors expressed at the cell membrane. Performing BAL in a reproducible manner is a hallmark of airway research in the mouse. Several procedures may be implemented. This unit describes a basic, rapid, inexpensive, and highly reproducible procedure to collect BAL fluid and cells that can be counted efficiently and reproducibly. Curr. Protoc. Mouse Biol. 2:167-175 © 2012 by John Wiley & Sons, Inc.

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Suppression of allergen-induced airway inflammation and immune response by the peroxisome proliferator-activated receptor-alpha agonist fenofibrate

Cited by 33 publications

References 23 publications

Peroxisome proliferator-activated receptor-α reduces inflammation and vascular leakage in a murine model of acute lung injury

Peroxisome proliferator-activated receptor-α reduces inflammation and vascular leakage in a murine model of acute lung injury

A Dissociated Glucocorticoid Receptor Modulator Reduces Airway Hyperresponsiveness and Inflammation in a Mouse Model of Asthma

Performing Bronchoalveolar Lavage in the Mouse

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