Involvement of distal airways in a chronic model of experimental asthma.

Summary Background Bronchial asthma is characterized by chronic airway inflammation and airway remodelling which occurs in both proximal and distal airways. These changes are associated with development of airway hyper-responsiveness and airflow limitation. Objective This study was aimed to analyse whether chronic inhalative allergen challenges in mice lead to morphological and physiological changes comparable with this phenotype. Methods For this purpose, BALB/c mice were systemically sensitized to ovalbumin (OVA) followed by aerosol allergen challenges on 2 consecutive days per week for 12 weeks. Results In chronically challenged mice, tissue inflammation in proximal as well as distal air…

Comparison of adjuvant and adjuvant-free murine experimental asthma models

Introduction The most widely used protocol for the induction of experimental allergic airway inflammation in mice involves sensitization by intraperitoneal (i.p.) injections of the antigen ovalbumin (OVA) used in conjunction with the adjuvant aluminium hydroxide (alum). Although adjuvants are frequently used, there are questions regarding the necessity of alum for murine asthma studies due to the non-physiological nature of this chemical. Objective The objective of this study was to compare experimental asthma phenotypes between adjuvant and adjuvant-free protocols of murine allergic airway inflammation in an attempt to develop a standardized alternative to adjuvant use. Method An adjuvant-…

Inflammation and remodelling of distal airways in a murine model of chronic experimental asthma

The Benefits of the Adjuvant-Free Murine Experimental Asthma Model. Adjuvant and Adjuvant-Free Protocols Produce Similar Phenotypes.

Anti-acids lead to immunological and morphological changes in the intestine of BALB/c mice similar to human food allergy

Abstract We have shown that anti-acid medication for treating dyspeptic disorders can block protein digestion and induce a higher risk for food sensitization. This mechanism was confirmed in human and animal studies on the humoral as well as the cellular level. Here we aimed to investigate the outcome of the treatment with the anti-acid drug sucralfate on the intestine in our murine model, assuming that morphological and immunological changes will occur. BALB/c mice were fed codfish extract plus sucralfate. Antibodies were examined in ELISA, RBL assay and Western blot. Quantitative morphological analysis of the intestine was performed by design-based stereology, focussing on epithelium, lam…

IL-17 and TNF-α Are Key Mediators of Moraxella catarrhalis Triggered Exacerbation of Allergic Airway Inflammation

Alterations of the airway microbiome is often associated with pulmonary diseases. For example, detection of the bacterial pathogen Moraxella catarrhalis in the upper airways is linked with an increased risk to develop or exacerbate asthma. However, the mechanisms by which M. cattarhalis augments allergic airway inflammation (AAI) remains unclear. We here characterized the cellular and soluble mediators of M. catarrhalis triggered excacerbation of AAI in wt and IL-17 deficient as well as in animals treated with TNF-alpha and IL-6 neutralizing antibodies. We compared the type of inflammatory response in M. catarrhalis infected, HDM-allergic and animals infected with M. catarrhalis at differen…

Reciprocal regulation of the Il9 locus by counteracting activities of transcription factors IRF1 and IRF4.

The T helper 9 (Th9) cell transcriptional network is formed by an equilibrium of signals induced by cytokines and antigen presentation. Here we show that, within this network, two interferon regulatory factors (IRF), IRF1 and IRF4, display opposing effects on Th9 differentiation. IRF4 dose-dependently promotes, whereas IRF1 inhibits, IL-9 production. Likewise, IRF1 inhibits IL-9 production by human Th9 cells. IRF1 counteracts IRF4-driven Il9 promoter activity, and IRF1 and IRF4 have opposing function on activating histone modifications, thus modulating RNA polymerase II recruitment. IRF1 occupancy correlates with decreased IRF4 abundance, suggesting an IRF1-IRF4-binding competition at the I…

Tc9 cells, a new subset of CD8+T cells, support Th2-mediated airway inflammation

Similar to T-helper (Th) cells, CD8(+) T cells also differentiate into distinct subpopulations. However, the existence of IL-9-producing CD8(+) T (Tc9) cells has not been elucidated so far. We show that murine CD8(+) T cells activated in the presence of IL-4 plus TGF-β develop into transient IL-9 producers characterized by specific IFN-γ and IL-10 expression patterns as well as by low cytotoxic function along with diminished expression of the CTL-associated transcription factors T-bet and Eomesodermin. Similarly to the CD4(+) counterpart, Tc9 cells required for their differentiation STAT6 and IRF4. Tc9 cells deficient for these master regulators displayed increased levels of Foxp3 that in t…