Suppression of cytokine expression by roflumilast and dexamethasone in a model of chronic asthma

Herbert, Cristan; Hettiaratchi, Anusha; Webb, Dianne C.; Thomas, Paul S.; Foster, Paul S.; Kumar, Rakesh K.

doi:10.1111/j.1365-2222.2008.02950.x

Cited by 60 publications

(71 citation statements)

References 48 publications

(58 reference statements)

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“…We modified exposure times to allow a temporal analysis of the effect of HDM on the regulation of miRNA expression in the airway wall. To achieve this, we separated the airway wall compartment from the parenchymal tissue by blunt microscopic dissection (25). Naive wild-type (WT) BALB/c mice were exposed to a single dose of HDM by directly instilling the allergen into the airways, and we then characterized the expression of miRNAs in the airway wall at 6, 12, and 24 h after challenge.…”

Section: Exposure Of the Airways To House Dust Mite Increases The Expmentioning

confidence: 99%

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Antagonism of microRNA-126 suppresses the effector function of T _H 2 cells and the development of allergic airways disease

Mattes

Collison²,

Plank³

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

402

370

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Allergic asthma is an inflammatory disease of the lung characterized by abnormal T helper-2 (T H2) lymphocyte responses to inhaled antigens. The molecular mechanisms leading to the generation of TH2 responses remain unclear, although toll-like receptors (TLRs) present on innate immune cells play a pivotal role in sensing molecular patterns and in programming adaptive T cell responses. Here we show that in vivo activation of TLR4 by house dust mite antigens leads to the induction of allergic disease, a process that is associated with expression of a unique subset of small, noncoding microRNAs. Selective blockade of microRNA (miR)-126 suppressed the asthmatic phenotype, resulting in diminished T H2 responses, inflammation, airways hyperresponsiveness, eosinophil recruitment, and mucus hypersecretion. miR-126 blockade resulted in augmented expression of POU domain class 2 associating factor 1, which activates the transcription factor PU.1 that alters T H2 cell function via negative regulation of GATA3 expression. In summary, this study presents a functional connection between miRNA expression and asthma pathogenesis, and our data suggest that targeting miRNA in the airways may lead to anti-inflammatory treatments for allergic asthma.animal model ͉ asthma ͉ inflammation ͉ microRNA ͉ TH2 cytokines

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Section: Exposure Of the Airways To House Dust Mite Increases The Expmentioning

confidence: 99%

“…Total RNA including miRNA was isolated with mirVana miRNA Isolation kit (Ambion) from lower airway tissue (25). Briefly, the trachea and lungs were isolated, and using two pairs of forceps, the parenchyma was separated from the larger airways by blunt dissection.…”

Section: Ahr Measurementmentioning

confidence: 99%

Antagonism of microRNA-126 suppresses the effector function of T _H 2 cells and the development of allergic airways disease

Mattes

Collison²,

Plank³

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

402

370

View full text Add to dashboard Cite

show abstract

“…Interestingly, part of the mechanism by which steroids produce anti-inflammatory effects appears to be related to suppression of cytokine expression within various cells. [20][21][22] For example, steroids are known to suppress IL-1B expression in various cell types.…”

Section: Inflammation and Continuous Glucose Monitoringmentioning

confidence: 99%

Role of Interleukin-1/Interleukin-1 Receptor Antagonist Family of Cytokines in Long-Term Continuous Glucose Monitoring In Vivo

Klueh

Antar

Qiao

et al. 2013

J Diabetes Sci Technol

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“…There are also reports using murine models showing that administration of roflumilast resulted in attenuation of asthma-like phenotypes (22,23). However, there is little in vivo evidence to suggest that the attenuation of the asthma phenotype results from biasing signaling toward the b 2 AR-Gas-cAMP pathway.…”

mentioning

confidence: 97%

Phosphodiesterase 4 Inhibitors Attenuate the Asthma Phenotype Produced by β₂-Adrenoceptor Agonists in Phenylethanolamine N-Methyltransferase–Knockout Mice

Forkuo

Kim

Thanawala

et al. 2016

Am J Respir Cell Mol Biol

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Mice lacking the endogenous b 2 -adrenoceptor (b 2 AR) agonist epinephrine (phenylethanolamine N-methyltransferase [PNMT]-knockout mice) are resistant to developing an "asthma-like" phenotype in an ovalbumin sensitization and challenge (Ova S/C) model, and chronic administration of b 2 AR agonists to PNMT-KO mice restores the phenotype. Based on these and other studies showing differential effects of various b 2 AR ligands on the asthma phenotype, we have speculated that the permissive effect of endogenous epinephrine and exogenous b 2 AR agonists on allergic lung inflammation can be explained by qualitative b 2 AR signaling. The b 2 AR can signal through at least two pathways: the canonical Gas-cAMP pathway and a b-arrestin-dependent pathway. Previous studies suggest that b-arrestin-2 is required for allergic lung inflammation. On the other hand, cell-based assays suggest antiinflammatory effects of Gas-cAMP signaling. This study was designed to test whether the in vitro antiinflammatory effects of phosphodiesterase 4 inhibitors, known to increase intracellular cAMP in multiple airway cell types, attenuate the asthma-like phenotype produced by the b 2 AR agonists formoterol and salmeterol in vivo in PNMT-KO mice, based on the hypothesis that skewing b 2 AR signaling toward Gas-cAMP pathway is beneficial. Airway inflammatory cells, epithelial mucus production, and airway hyperresponsiveness were quantified. In Ova S/C PNMT-KO mice, formoterol and salmeterol restored the asthma-like phenotype comparable to Ova S/C wild-type mice. However, coadministration of either roflumilast or rolipram attenuated this formoterol-or salmeterol-driven phenotype in Ova S/C PNMT-KO. These findings suggest that amplification of b 2 AR-mediated cAMP by phosphodiesterase 4 inhibitors attenuates the asthma-like phenotype promoted by b-agonists.

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Suppression of cytokine expression by roflumilast and dexamethasone in a model of chronic asthma

Cited by 60 publications

References 48 publications

Antagonism of microRNA-126 suppresses the effector function of T _H 2 cells and the development of allergic airways disease

Antagonism of microRNA-126 suppresses the effector function of T _H 2 cells and the development of allergic airways disease

Role of Interleukin-1/Interleukin-1 Receptor Antagonist Family of Cytokines in Long-Term Continuous Glucose Monitoring In Vivo

Phosphodiesterase 4 Inhibitors Attenuate the Asthma Phenotype Produced by β₂-Adrenoceptor Agonists in Phenylethanolamine N-Methyltransferase–Knockout Mice

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Suppression of cytokine expression by roflumilast and dexamethasone in a model of chronic asthma

Cited by 60 publications

References 48 publications

Antagonism of microRNA-126 suppresses the effector function of T H 2 cells and the development of allergic airways disease

Antagonism of microRNA-126 suppresses the effector function of T H 2 cells and the development of allergic airways disease

Role of Interleukin-1/Interleukin-1 Receptor Antagonist Family of Cytokines in Long-Term Continuous Glucose Monitoring In Vivo

Phosphodiesterase 4 Inhibitors Attenuate the Asthma Phenotype Produced by β2-Adrenoceptor Agonists in Phenylethanolamine N-Methyltransferase–Knockout Mice

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Product

Resources

About

Antagonism of microRNA-126 suppresses the effector function of T _H 2 cells and the development of allergic airways disease

Antagonism of microRNA-126 suppresses the effector function of T _H 2 cells and the development of allergic airways disease

Phosphodiesterase 4 Inhibitors Attenuate the Asthma Phenotype Produced by β₂-Adrenoceptor Agonists in Phenylethanolamine N-Methyltransferase–Knockout Mice