Comparison of allergic lung disease in three mouse strains after systemic or mucosal sensitization with ovalbumin antigen
(Impact Factor: 2.23).
03/2009; 61(3):199-207. DOI: 10.1007/s00251-008-0353-8
Murine models of allergic lung disease have many similar traits to asthma in humans and can be used to investigate mechanisms
of allergic sensitization and susceptibility factors associated with disease severity. The purpose of this study was to determine
strain differences in allergic airway inflammation, immunoglobulin production, and changes in respiratory responses between
systemic and mucosal sensitization routes in BALB/cJ, FVB/NJ, and C57BL/6J, and to provide correlations between immune and
pathophysiological endpoints. After a single intranasal ovalbumin (OVA) challenge, all three strains of mice systemically
sensitized with OVA and adjuvant exhibited higher airflow limitation than non-sensitized mice. No changes were seen in mice
that were pre-sensitized via the nose with OVA. Systemic sensitization resulted in an elevated response to methacholine (MCH)
in BALB/cJ and FVB/NJ mice and elevated total and OVA-specific IgE levels and pulmonary eosinophils in all three strains.
The mucosal sensitization and challenge produced weaker responses in the same general pattern with the C57BL/6J strain producing
less serum IgE, IL5, IL13, and eosinophils in lung fluid than the other two strains. The converse was found for IL6 where
the C57BL/6J mice had more than twice the amount of this cytokine. The results show that the FVB/NJ and BALB/cJ mice are higher
Th2-responders than the C57BL/6J mice and that the levels of pulmonary eosinophilia and cytokines did not fully track with
MCH responsiveness. These differences illustrate the need to assess multiple endpoints to provide clearer associations between
immune responses and type and severity of allergic lung disease.
Available from: Shaopeng Yuan
- "Because of the possibility that insufficient backcrossing could influence physiological and inflammatory outcomes in mouse models of asthma 24, 25, we repeated the Aspergillus allergen protocol in mice backcrossed six times into a C57BL/6 background (F6). In these repeat experiments we simultaneously backcrossed the mice into a 4get background, because the IL-4-IRES-eGFP (4get) reporter allows monitoring of IL-4 expressing cell trafficking and cell sorting. "
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ABSTRACT: The pathophysiology of asthma involves allergic inflammation and remodelling in the airway and airway hyperresponsiveness (AHR) to cholinergic stimuli, but many details of the specific underlying cellular and molecular mechanisms remain unknown. Periostin is a matricellular protein with roles in tissue repair following injury in both the skin and heart. It has recently been shown to be up-regulated in the airway epithelium of asthmatics and to increase active TGF-β. Though one might expect periostin to play a deleterious role in asthma pathogenesis, to date its biological role in the airway is unknown.
To determine the effect of periostin deficiency on airway responses to inhaled allergen.
In vivo measures of airway responsiveness, inflammation, and remodelling were made in periostin deficient mice and wild-type controls following repeated intranasal challenge with Aspergillus fumigatus antigen. In vitro studies of the effects of epithelial cell-derived periostin on murine T cells were also performed.
Surprisingly, compared with wild-type controls, periostin deficient mice developed increased AHR and serum IgE levels following allergen challenge without differences in two outcomes of airway remodelling (mucus metaplasia and peribronchial fibrosis). These changes were associated with decreased expression of TGF-β1 and Foxp3 in the lungs of periostin deficient mice. Airway epithelial cell-derived periostin-induced conversion of CD4(+) CD25(-) cells into CD25(+) , Foxp3(+) T cells in vitro in a TGF-β dependent manner.
Allergen-induced increases in serum IgE and bronchial hyperresponsiveness are exaggerated in periostin deficient mice challenged with inhaled aeroallergen. The mechanism of periostin's effect as a brake on allergen-induced responses may involve augmentation of TGF-β-induced T regulatory cell differentiation.
Clinical & Experimental Allergy 08/2011; 42(1):144-55. DOI:10.1111/j.1365-2222.2011.03840.x · 4.77 Impact Factor
Available from: ncbi.nlm.nih.gov
- "The predominant inflammatory cells recruited into asthmatic lung tissues are eosinophils (Srelts et al., 1998; Kim et al., 2007). Eosinophilia in asthmatic BAL fluid is also associated with the production of IL-5, which plays a critical role in the differentiation, infiltration, activation of pulmonary eosinophils (Kim et al., 2007; Zhu and Gilmour, 2009) and VCAM-1 expression. Therefore, our data suggest that R2 peptide may reduce the numbers and infiltration of eosinophils by inhibiting IL-5 expression, and may reduce the trafficking of other inflammatory cells including eosinophils by inhibiting the adhesion molecule VCAM-1 expressed via Th2-mediated cytokines, and by inhibiting the chemokines such as IL-8 and CCL5, produced via NF-kB activation. "
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ABSTRACT: Transglutaminase 2 (TGase 2) expression is increased in inflammatory diseases, and TGase 2 inhibitors block these increases. We examined whether the R2 peptide inhibited the expression of TGase 2 in a mouse model of inflammatory allergic asthma.
C57BL/6 mice were sensitized and challenged by ovalbumin (OVA) to induce asthma. OVA-specific serum IgE and leukotrienes (LTs) levels were measured by enzyme-linked immunosorbent assay. Recruitment of inflammatory cells into bronchoalveolar lavage (BAL) fluid or lung tissues and goblet cell hyperplasia were assessed histologically. Airway hyperresponsiveness was determined in a barometric plethysmographic chamber. Expression of TGase 2, eosinophil major basic protein (EMBP), the adhesion molecule vascular cell adhesion molecule-1, Muc5ac and phospholipase A(2) (PLA(2) ) protein were determined by Western blot. Expression of mRNAs of Muc5ac, cytokines, matrix metalloproteinases (MMPs) and tissue inhibitors of MMPs (TIMPs) were measured by reverse transcriptase-polymerase chain reaction and nuclear factor-κB (NF-κB) by electrophoretic mobility shift assay.
R2 peptide reduced OVA-specific IgE levels; the number of total inflammatory cells, macrophages, neutrophils, lymphocytes and eosinophils in BAL fluid and the number of goblet cells. Airway hyperresponsiveness, TGase 2 and EMBP levels, mRNA levels of interleukin (IL)-4, IL-5, IL-6, IL-8, IL-13, RANTES, tumour necrosis factor-α, and MMP2/9, Muc5ac, NF-κB activity, PLA(2) activity and expressions, and LT levels in BAL cells and lung tissues were all reduced by R2 peptide. R2 peptide also restored expression of TIMP1/2.
R2 peptide reduced allergic responses by regulating NF-κB/TGase 2 activity in a mouse model of allergic asthma. This peptide may be useful in the treatment of allergic asthma.
British Journal of Pharmacology 01/2011; 162(1):210-25. DOI:10.1111/j.1476-5381.2010.01033.x · 4.84 Impact Factor
Available from: Jeroen Vanoirbeek
- "Although exposed to similar allergic stimuli, not all humans develop allergic or occupational asthma. The etiology of asthma is complex and is associated with a combination of immune, genetic, environmental and socio-economic factors , . "
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ABSTRACT: The development of occupational asthma is the result of interactions between environmental factors and individual susceptibility. We assessed how our model of chemical-induced asthma is influenced by using different mouse strains.
On days 1 and 8, male mice of 7 different strains (BALB/c, BP/2, A/J, C57Bl/6, DBA/2, CBA and AKR) were dermally treated with toluene-2,4-diisocyanate (TDI) (0.3%) or vehicle (acetone/olive oil, AOO, 2:3) on each ear (20 microl). On day 15, they received an oropharyngeal instillation of TDI (0.01%) or AOO (1:4). Airway reactivity to methacholine, total and differential cell counts in bronchoalveolar lavage (BAL) and total serum IgE and IgG(2a) levels were measured. Lymphocyte subpopulations in auricular lymph nodes and in vitro release of cytokines by ConA stimulated lymphocytes were assessed. In TDI-sensitized and challenged mice, airway hyper-reactivity was only observed in BALB/c, BP/2, A/J and AKR mice; airway inflammation was most pronounced in BALB/c mice; numbers of T-helper (CD4(+)), T-activated (CD4(+)CD25(+)), T-cytotoxic (CD8(+)) and B- lymphocytes (CD19(+)) were increased in the auricular lymph nodes of BALB/c, BP/2, A/J and CBA mice; elevated concentrations of IL-4, IL-10, IL-13 and IFN-gamma were detected in supernatant of lymphocytes from BALB/c, BP/2, A/J, C57Bl/6 and CBA mice cultured with concanavaline A, along with an increase in total serum IgE.
The used mouse strain has considerable and variable impacts on different aspects of the asthma phenotype. The human phenotypical characteristics of chemically-induced occupational asthma were best reproduced in Th2-biased mice and in particular in BALB/c mice.
PLoS ONE 09/2010; 5(9):e12581. DOI:10.1371/journal.pone.0012581 · 3.23 Impact Factor
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