Modeling Asthma in Mice

Hirota, Jeremy A.; Hackett, Tillie-Louise; Inman, Mark D.; Knight, Darryl A.

doi:10.1165/rcmb.2010-0146tr

Cited by 28 publications

(13 citation statements)

References 84 publications

(96 reference statements)

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“…We believe it is important to report these statin effects on murine airway epithelial cells in order to refine future work in this field, at least as relevant to mouse models that utilize the airway epithelium. Furthermore, this in vitro ALI/biphasic model is an efficient and experimentally accessible cell culture system that mimics ‘near-physiological’ conditions and encourages the testing of a wider range of statin doses on airway epithelial function in general [49,50]. This facilitates the direct study of statins’ molecular mechanisms of action, as compared to less direct animal models with the attendant complexities of the in vivo environment.…”

Section: Discussionmentioning

confidence: 99%

Differential effects of simvastatin on IL-13-induced cytokine gene expression in primary mouse tracheal epithelial cells

et al. 2012

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BackgroundAsthma causes significant morbidity worldwide in adults and children alike, and incurs large healthcare costs. The statin drugs, which treat hyperlipidemia and cardiovascular diseases, have pleiotropic effects beyond lowering cholesterol, including immunomodulatory, anti-inflammatory, and anti-fibrotic properties which may benefit lung health. Using an allergic mouse model of asthma, we previously demonstrated a benefit of statins in reducing peribronchiolar eosinophilic inflammation, airway hyperreactivity, goblet cell hyperplasia, and lung IL-4 and IL-13 production.ObjectivesIn this study, we evaluated whether simvastatin inhibits IL-13-induced pro-inflammatory gene expression of asthma-related cytokines in well-differentiated primary mouse tracheal epithelial (MTE) cell cultures. We hypothesized that simvastatin reduces the expression of IL-13-inducible genes in MTE cells.MethodsWe harvested tracheal epithelial cells from naïve BALB/c mice, grew them under air-liquid interface (ALI) cell culture conditions, then assessed IL-13-induced gene expression in MTE cells using a quantitative real-time PCR mouse gene array kit.ResultsWe found that simvastatin had differential effects on IL-13-mediated gene expression (inhibited eotaxin-1; MCP-1,-2,-3; and osteopontin (SPP1), while it induced caspase-1 and CCL20 (MIP-3α)) in MTE cells. For other asthma-relevant genes such as TNF, IL-4, IL-10, CCL12 (MCP-5), CCL5 (RANTES), and CCR3, there were no significant IL-13-inducible or statin effects on gene expression.ConclusionsSimvastatin modulates the gene expression of selected IL-13-inducible pro-inflammatory cytokines and chemokines in primary mouse tracheal epithelial cells. The airway epithelium may be a viable target tissue for the statin drugs. Further research is needed to assess the mechanisms of how statins modulate epithelial gene expression.

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Section: Discussionmentioning

confidence: 99%

Differential effects of simvastatin on IL-13-induced cytokine gene expression in primary mouse tracheal epithelial cells

et al. 2012

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“…The fluoric alcohols (e.g., 2,2,2-trifluoroethanol and HFIP) have been widely used to simulate hydro-phobic environments and to establish the in vivo conformations of many peptides that either reside within or are bound to membranes. [51][52][53][54][55] The CD results have shown that Yang et al…”

Section: Tertiary Structure Of Cav-1(93-126) In 60%hfip-d 2 Aqueous Smentioning

confidence: 99%

Structural study of caveolin‐1 intramembrane domain by circular dichroism and nuclear magnetic resonance

Yang

Dong

et al. 2015

Biopolymers

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Caveolin-1 is a main structural component of caveolae and essential for the invagination of caveolae by forming a hairpin-shaped structure in the membrane-inserting domain (residues, 102-122). In this article, we determined the tertiary structures of the peptides comprising residues 93-126 and 101-126 of caveolin-1 in 1,1,1,3,3,3-hexafluoro-2-propanol (HFIP) aqueous solution and sodium dodecyl sulfate (SDS) micelles, respectively, by nuclear magnetic resonance (NMR) study. The self-association of the peptides in SDS and dodecylphosphocholine (DPC) micelles was also studied by circular dichroism (CD), NMR, and sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) techniques. Our results indicated that both peptides form a helix-break-helix structure with two helices spanning over Leu103-Phe107 and Ile117-His126 and a loop ranging over Gly108-Gly116. The longer peptide 93-126 showed a stronger propensity to aggregate than the shorter peptide 101-126 in the micelles. Our results suggested that the glycine residues at positions 108 and 116 are important for the break of the helical structure of the membrane-inserting domain and the segment Thr93-Arg101 flanking the membrane-inserting domain may play a role in the self-association of the caveolin-1 protein at cellular membrane.

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“…The classic model involves the sensitization and challenge to ovalbumin (OVA) [150], followed by collection of tissue, BAL fluid, or other samples at key time points following challenge. Genetic manipulation of the mouse, adoptive transfer of selected lymphocytes, or other treatments can modify airway inflammation.…”

Section: Apoptosis In Airway Epithelium In Diseasementioning

confidence: 99%

Apoptosis and the Airway Epithelium

White

2011

Journal of Allergy

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The airway epithelium functions as a barrier and front line of host defense in the lung. Apoptosis or programmed cell death can be elicited in the epithelium as a response to viral infection, exposure to allergen or to environmental toxins, or to drugs. While apoptosis can be induced via activation of death receptors on the cell surface or by disruption of mitochondrial polarity, epithelial cells compared to inflammatory cells are more resistant to apoptotic stimuli. This paper focuses on the response of airway epithelium to apoptosis in the normal state, apoptosis as a potential regulator of the number and types of epithelial cells in the airway, and the contribution of epithelial cell apoptosis in important airways diseases.

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Modeling Asthma in Mice

Cited by 28 publications

References 84 publications

Differential effects of simvastatin on IL-13-induced cytokine gene expression in primary mouse tracheal epithelial cells

Differential effects of simvastatin on IL-13-induced cytokine gene expression in primary mouse tracheal epithelial cells

Structural study of caveolin‐1 intramembrane domain by circular dichroism and nuclear magnetic resonance

Apoptosis and the Airway Epithelium

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