Pulmonary Endotoxin Tolerance Protects against Cockroach Allergen-Induced Asthma-Like Inflammation in a Mouse Model

Natarajan, Sudha; Kim, Jiyoun; Bouchard, Jacqueline; Cruikshank, William W.; Remick, Daniel G.

doi:10.1159/000330896

Cited by 12 publications

(10 citation statements)

References 94 publications

(56 reference statements)

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“…sensitisation with LPS-contaminated OVA, the observed airway inflammation was dependent on IL-17 [39]. In addition, it has been reported that tolerisation to LPS prior to sensitisation can prevent eosinophilic infiltration in BAL [40]. It is thus likely that LPS, or other constituents of the CDE, promote the mixed type of airway response seen in our cat allergen-induced asthma model.…”

Section: Discussionmentioning

confidence: 80%

Development of a Mouse Model for Chronic Cat Allergen-Induced Asthma

Grundström

Saarne

Kemi³

et al. 2014

Int Arch Allergy Immunol

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Background: Allergic asthma is a chronic inflammatory airway disease caused by exposure to airborne allergens. In order to develop novel therapies for allergic asthma, models that are relevant to human disease are needed. Methods: Female BALB/c mice were presensitised subcutaneously with alum-adsorbed recombinant cat allergen Fel d 1, followed by intranasal challenges with cat dander extract spiked with recombinant Fel d 1 for 7 weeks. For reference, mice were presensitised and challenged with ovalbumin following the same protocol. Airway hyperresponsiveness, serum antibodies, airway inflammation and cell infiltration, and cytokines in lung tissue and bronchoalveolar lavage were measured. Results: Mice presensitised with recombinant Fel d 1 and challenged with cat dander extract or presensitised and challenged with ovalbumin showed airway hyperresponsiveness in response to metacholine. Mice of the cat allergen model showed influx of neutrophils, eosinophils and lymphocytes in bronchoalveolar lavage, combined with increased levels of IL-17a and increased IL-4 mRNA expression in lung tissue. In contrast, mice sensitised and challenged with ovalbumin showed a predominant influx of eosinophils in bronchoalveolar lavage and had an increased expression of IL-5 in lung tissue. Both protocols induced features of lung tissue remodelling and allergen-specific antibody responses. Conclusions: The presented mouse model for cat allergen-induced asthma exhibits hallmarks of chronic allergic asthma, like airway hyperresponsiveness, a mixed neutrophilic/eosinophilic infiltration in bronchoalveolar lavage, expression of IL-17a and signs of remodelling in lung tissue. The model will provide a relevant platform for the development of novel treatment strategies.

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Section: Discussionmentioning

confidence: 80%

Development of a Mouse Model for Chronic Cat Allergen-Induced Asthma

Grundström

Saarne

Kemi³

et al. 2014

Int Arch Allergy Immunol

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“…Increased endotoxin concentrations were found in the house dust of farms compared to urban environments, suggesting a protective effect against the development of atopy [50], possibly by causing Th1 domination in the immune system [51,52]. However, this protective effect of the farm environment may exist only in the early years of childhood [53].…”

Section: Bacterial Lps/bacterial Endotoxinmentioning

confidence: 99%

“…However, this protective effect of the farm environment may exist only in the early years of childhood [53]. In a mouse model, pulmonary endotoxin tolerance was found to be protective against cockroach allergen-induced asthma-like inflammation [52]. Obesity was found to be associated with the development of atopic dermatitis only in children.…”

Section: Bacterial Lps/bacterial Endotoxinmentioning

confidence: 99%

The Immunomodulatory Role of Bile Acids

Sipka

Bruckner

2014

Int Arch Allergy Immunol

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Enzymatic oxidation of cholesterol generates numerous distinct bile acids which function both as detergents that facilitate the digestion and absorption of dietary lipids and as hormones that activate five distinct receptors. Activation of these receptors alters gene expression in multiple tissues, leading to changes not only in bile acid metabolism but also in glucose homeostasis, lipid and lipoprotein metabolism, energy expenditure, intestinal motility, bacterial growth, inflammation, and in the liver-gut axis. This review focuses on the present knowledge regarding the physiologic and pathologic role of bile acids and their immunomodulatory role, with particular attention to bacterial lipopolysaccharides (endotoxins) and bile acid and immunological disorders. The specific role that bile acids play in the regulation of innate immunity, various systemic inflammations, inflammatory bowel diseases, allergy, psoriasis, cholestasis, obesity, metabolic syndrome, alcoholic liver disease, and colon cancer will be reviewed.

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“…Shi et al studied leukocyte distribution in the BAL fluid using aerosolized OVA-challenged mice and they found that the number of inflammatory cells was markedly reduced by persistent or intermittent OVA challenges, which was related to the development of allergen-dependent immune tolerance. Natarajan et al used LPS to induce long-lasting immune tolerance in mice, and they found lessened inflammation associated with asthma caused by cockroach allergens [8]. …”

Section: Discussionmentioning

confidence: 99%

Re-Challenge with Ovalbumin Failed to Induce Bronchial Asthma in Mice with Eosinophilic Bronchitis

2013

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ObjectiveTo investigate whether eosinophilic bronchitis without airway hyperresponsiveness will develop bronchial asthma in allergic mice.MethodsMice were sensitized with OVA on days 0, 7, and 14, challenged on days 21 to 23 (1st OVA challenge), and re-challenged on days 46 to 48 (2nd OVA challenge), intranasally with 10 (the EB group) and 200 (the AS group) μg OVA. Lung resistance (RL) was assessed 24 h after each challenge and on day 45 followed by analysis of leukocyte distribution in the bronchoalveolar lavage (BAL) fluid and histological examination.ResultsTwenty-four hours after the 1st OVA challenge, aerosolized methacholine caused a dose-dependent increase in RL in all groups. At doses ≥1.56 mg/mL, RL in the AS group was significantly higher than that of the NS-1 group (P<0.01 or 0.05) and at doses ≥12.5 mg/mL, RL was markedly higher in the AS group than that of the EB group (P<0.01). The percentage of eosinophils in both the EB group and the AS group was markedly higher than that of the control group. Twenty-four hours after the 2nd OVA challenge, at doses ≤12.5 mg/mL, there was no significant difference in RL among all groups (P>0.05). At doses ≥12.5 mg/mL, RL in the AS group was significantly higher than that of the control group and EB group (P<0.01 or 0.05). The percentage of eosinophils in the AS group was noticeably higher than that of the EB group(P<0.05). Furthermore, there was apparent infiltration by inflammatory cells, predominantly eosinophils, into the sub-epithelial region of the bronchus and the bronchioles and around the vessels in the EB and AS group.ConclusionRe-challenge with low doses of ovalbumin did not increase airway reactivity and failed to induce bronchial asthma in mice with ovalbumin-induced EB.

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Pulmonary Endotoxin Tolerance Protects against Cockroach Allergen-Induced Asthma-Like Inflammation in a Mouse Model

Cited by 12 publications

References 94 publications

Development of a Mouse Model for Chronic Cat Allergen-Induced Asthma

Development of a Mouse Model for Chronic Cat Allergen-Induced Asthma

The Immunomodulatory Role of Bile Acids

Re-Challenge with Ovalbumin Failed to Induce Bronchial Asthma in Mice with Eosinophilic Bronchitis

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