Mouse models of asthma: a comparison between C57BL/6 and BALB/c strains regarding bronchial responsiveness, inflammation, and cytokine production

Guéders, Maud; Paulissen, Geneviève; Crahay, Céline; Quesada-Calvo, Florence; Hacha, Jonathan; Hove, Chris Van; Tournoy, Kurt G.; Louis, Renaud; Foidart, Jean-Michel; Noël, Agnès; Cataldo, Didier

doi:10.1007/s00011-009-0054-2

Cited by 178 publications

(149 citation statements)

References 32 publications

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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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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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“…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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“…C57BL/6 mice tend to have a reduced AHR response in comparison to BALB/c mice (15,16), and this was the case in response to Pneumocystis as well. The C57BL/6 mice we tested required a higher dose of methacholine than did BALB/c mice (30 versus 20 mg/ml aerosolization) to reach significantly elevated Penh values.…”

Section: Time Course Of Ahr In Balb/c Versus C57bl/6 Micementioning

confidence: 91%

Pneumocystis Elicits a STAT6-Dependent, Strain-Specific Innate Immune Response and Airway Hyperresponsiveness

Swain

Meissner²,

Siemsen³

et al. 2012

Am J Respir Cell Mol Biol

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It is widely held that exposure to pathogens such as fungi can be an agent of comorbidity, such as exacerbation of asthma or chronic obstructive pulmonary disease. Although many studies have examined allergic responses to fungi and their effects on pulmonary function, the possible pathologic implications of the early innate responses to fungal pathogens have not been explored. We examined early responses to the atypical fungus Pneumocystis in two common strains of mice in terms of overall immunological response and related pathology, such as cell damage and airway hyperresponsiveness (AHR). We found a strong strain-specific response in BALB/c mice that included recruitment of neutrophils, NK, NKT, and CD4 T cells. This response was accompanied by elevated indicators of lung damage (bronchoalveolar lavage fluid albumin and LDH) and profound AHR. This early response was absent in C57BL/6 mice, although both strains exhibited a later response associated with the clearance of Pneumocystis. We found that this AHR could not be attributed exclusively to the presence of recruited neutrophils, NKT, NK, or CD4 cells or to the actions of IFN-g or IL-4. However, in the absence of STAT6 signaling, AHR and inflammatory cell recruitment were virtually absent. Gene expression analysis indicated that this early response included activation of several transcription factors that could be involved in pulmonary remodeling. These results show that exposure to a fungus such as Pneumocystis can elicit pulmonary responses that may contribute to morbidity, even without prior sensitization, in the context of certain genetic backgrounds.Keywords: STAT6; airway hyperresponsiveness; Pneumocystis; pulmonary inflammation; strain-specificThe immunological response to respiratory pathogens is normally calibrated to eliminate an infection without causing overt collateral damage to the respiratory tissue. In spite of this, an overexuberant or misdirected immune response can have pathological outcomes. This can range from phenomena that are transient and typically moderate, such as elevated airway hyperresponsiveness (AHR), to those that are permanent and progressive, such as pulmonary fibrosis. The health effects of these immunological responses depend on the context of the infection; those that are comorbid with other acute or chronic pulmonary conditions may incite serious respiratory distress in that context when otherwise they might have little noticeable effect.One area in which the effects of comorbid respiratory illnesses are especially relevant is that of exacerbation of preexisting asthma or chronic obstructive pulmonary disease (COPD). Many potential pathogens have been implicated as causing exacerbation; the most well known are various viruses, including rhinovirus, metapneumovirus, and respiratory syncytial virus (1). Several respiratory bacteria, most notably the atypical bacteria Mycoplasma pneumoniae and Chlamydia pneumoniae, have also been implicated in the exacerbation of asthma symptoms (2). Common fungi have also been widely imp...

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Mouse models of asthma: a comparison between C57BL/6 and BALB/c strains regarding bronchial responsiveness, inflammation, and cytokine production

Cited by 178 publications

References 32 publications

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

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

Pneumocystis Elicits a STAT6-Dependent, Strain-Specific Innate Immune Response and Airway Hyperresponsiveness

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