Comparison of Acute Inflammatory and Chronic Structural Asthma-Like Responses between C57BL/6 and BALB/c Mice

Hove, Chris L. Van; Maes, Tania; Cataldo, Didier; Guéders, Maud; Palmans, Els; Joos, Guy; Tournoy, Kurt G.

doi:10.1159/000199715

Cited by 63 publications

(59 citation statements)

References 82 publications

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“…We used the immunodominant allergen from the Dermatophagoides pteronyssinus species of house dust mite (HDM), Der p 1, a relevant human allergen. As expected based on previous studies (8,11), C57BL/6J mice exhibited a stronger inflammatory response than did BALB/cJ mice, yet showed a striking decrease in airway responsiveness to methacholine. Using gene expression analysis, we identified a set of down-regulated G-protein-coupled receptors (GPCRs) involved in airway smooth muscle contraction that may mediate this response.…”

supporting

confidence: 89%

“…For example, the two most commonly used inbred strains, C57BL/6J and BALB/cJ, differ in ovalbumin models of allergic disease (10,11). Furthermore, the link between allergic inflammation and AHR is also strain-dependent and model-dependent, with certain strains manifesting either or both phenotypes as a function of the induction of different allergen-response pathways (e.g., IL-4/ CD4 1 T-cell-dependent pathways (12) versus IL-5/eosinophildependent pathways (13)), and of the route or timing of exposure (9).…”

mentioning

confidence: 99%

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Strain-Dependent Genomic Factors Affect Allergen-Induced Airway Hyperresponsiveness in Mice

Kelada

Wilson

Tavarez

et al. 2011

Am J Respir Cell Mol Biol

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Asthma is etiologically and clinically heterogeneous, making the genomic basis of asthma difficult to identify. We exploited the straindependence of a murine model of allergic airway disease to identify different genomic responses in the lung. BALB/cJ and C57BL/6J mice were sensitized with the immunodominant allergen from the Dermatophagoides pteronyssinus species of house dust mite (Der p 1), without exogenous adjuvant, and the mice then underwent a single challenge with Der p 1. Allergic inflammation, serum antibody titers, mucous metaplasia, and airway hyperresponsiveness were evaluated 72 hours after airway challenge. Whole-lung gene expression analyses were conducted to identify genomic responses to allergen challenge. Der p 1-challenged BALB/cJ mice produced all the key features of allergic airway disease. In comparison, C57BL/6J mice produced exaggerated Th2-biased responses and inflammation, but exhibited an unexpected decrease in airway hyperresponsiveness compared with control mice. Lung gene expression analysis revealed genes that were shared by both strains and a set of down-regulated genes unique to C57BL/6J mice, including several G-protein-coupled receptors involved in airway smooth muscle contraction, most notably the M2 muscarinic receptor, which we show is expressed in airway smooth muscle and was decreased at the protein level after challenge with Der p 1. Murine strain-dependent genomic responses in the lung offer insights into the different biological pathways that develop after allergen challenge. This study of two different murine strains demonstrates that inflammation and airway hyperresponsiveness can be decoupled, and suggests that the downmodulation of expression of G-protein-coupled receptors involved in regulating airway smooth muscle contraction may contribute to this dissociation.

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confidence: 89%

mentioning

confidence: 99%

Strain-Dependent Genomic Factors Affect Allergen-Induced Airway Hyperresponsiveness in Mice

Kelada

Wilson

Tavarez

et al. 2011

Am J Respir Cell Mol Biol

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“…In this context, OVA-challenged Mmp9-deficient mice displayed lower eosinophilia and hyperresponsiveness (9), whereas other authors using a different experimental protocol (far higher doses of allergen) reported increased eosinophilia in Mmp9 KO mice (13). The importance of the experimental protocol used to assess a phenotype in mice is further highlighted by various reports stating that there are important differences when considering various strains of mice (32,33). Notably, the present study provides evidence for similar exacerbated eosinophilia and increased AHR in Adamts12 2/2 mice of similar background, sensitized and challenged with two different allergens, the "classical" OVA and the very significant and widespread allergen for human asthmatics, HDM.…”

Section: Discussionmentioning

confidence: 99%

Control of Allergen-Induced Inflammation and Hyperresponsiveness by the Metalloproteinase ADAMTS-12

Paulissen

Hour

Rocks

et al. 2012

The Journal of Immunology

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A disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS) constitute a family of endopeptidases related to matrix metalloproteinases. These proteinases have been largely implicated in tissue remodeling associated with pathological processes. Among them, ADAMTS12 was identified as an asthma-associated gene in a human genome screening program. However, its functional implication in asthma is not yet documented. The present study aims at investigating potential ADAMTS-12 functions in experimental models of allergic airways disease. Two different in vivo protocols of allergen-induced airways disease were applied to the recently generated Adamts12-deficient mice and corresponding wild-type mice. In this study, we provide evidence for a protective effect of ADAMTS-12 against bronchial inflammation and hyperresponsiveness. In the absence of Adamts12, challenge with different allergens (OVA and house dust mite) led to exacerbated eosinophilic inflammation in the bronchoalveolar lavage fluid and in lung tissue, along with airway dysfunction assessed by increased airway responsiveness following methacholine exposure. Furthermore, mast cell counts and ST2 receptor and IL-33 levels were higher in the lungs of allergen-challenged Adamts12-deficient mice. The present study provides, to our knowledge, the first experimental evidence for a contribution of ADAMTS-12 as a key mediator in airways disease, interfering with immunological processes leading to inflammation and airway hyperresponsiveness.

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“…In the present study, we performed our experiments using OVA in C57BL/6 mice who have been shown to be less responsive to metacholine compared with other mouse strains such as BALB/c (38,39). It was further suggested that the genetic background of mice influences several aspects of the acute allergic phenotype, including airway hyperresponsiveness (38,39).…”

Section: Discussionmentioning

confidence: 97%

Nuclear Receptor Nur77 Attenuates Airway Inflammation in Mice by Suppressing NF-κB Activity in Lung Epithelial Cells

Kurakula

Vos

Logiantara

et al. 2015

The Journal of Immunology

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Allergic asthma is characterized by persistent chronic airway inflammation, which leads to mucus hypersecretion and airway hyperresponsiveness. Nuclear receptor Nur77 plays a pivotal role in distinct immune and inflammatory cells and is expressed in eosinophils and lung epithelium. However, the role of Nur77 in allergic airway inflammation has not been studied so far. In the present study, we determined the role of Nur77 in airway inflammation using a murine model of OVA-induced allergic airway inflammation. We found that OVA-challenged Nur77 knockout (KO) mice show significantly enhanced infiltration of inflammatory cells, including eosinophils and lymphocytes, and aggravated mucus production. The infiltration of macrophages is limited in this model and was similar in wild-type and Nur77 KO mice. Higher levels of Th2 cytokines were found in bronchoalveolar lavage fluid and draining lymph node cells of Nur77-KO mice, as well as increased serum IgG1 and IgG2a levels. Knockdown of Nur77 in human lung epithelial cells resulted in a marked increase in IκBα phosphorylation, corresponding with elevated NF-κB activity, whereas Nur77 overexpression decreased NF-κB activity. Consistently, Nur77 significantly decreased mRNA levels of inflammatory cytokines and Muc5ac expression and also attenuated mucus production in lung epithelial cells. To further corroborate these findings, we searched for association of single nucleotide polymorphisms in Nur77 gene with asthma and with the severity of bronchial hyperresponsiveness. We identified three Nur77 single nucleotide polymorphisms showing association with severity of bronchial hyperresponsiveness in asthma patients. Collectively, these findings support a protective role of Nur77 in OVA-induced airway inflammation and identify Nur77 as a novel therapeutic target for airway inflammation.

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Comparison of Acute Inflammatory and Chronic Structural Asthma-Like Responses between C57BL/6 and BALB/c Mice

Cited by 63 publications

References 82 publications

Strain-Dependent Genomic Factors Affect Allergen-Induced Airway Hyperresponsiveness in Mice

Strain-Dependent Genomic Factors Affect Allergen-Induced Airway Hyperresponsiveness in Mice

Control of Allergen-Induced Inflammation and Hyperresponsiveness by the Metalloproteinase ADAMTS-12

Nuclear Receptor Nur77 Attenuates Airway Inflammation in Mice by Suppressing NF-κB Activity in Lung Epithelial Cells

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