Differential Regulation of Inflammation and Immunity in Mild and Severe Experimental Asthma

Abstract

This study aimed at exploring innate and adaptive immunity in allergic asthma by investigation of mRNA expression of pattern recognition receptors, T-cell-specific cytokines, and transcription factors. Mouse models for mild and severe asthma, with similar pathological characteristics observed in humans, were used to study the involved inflammatory markers as a first step in the development of phenotype-directed treatment approaches. In the mild model, mice were sensitized to ovalbumin-Imject Alum and challenged with ovalbumin. In the severe model, mice were sensitized to trinitrophenyl-conjugated ovalbumin and challenged with trinitrophenyl-ovalbumin/IgE immune complex. Pulmonary airway inflammation and mRNA expression of Toll-like receptors (TLRs), NOD-like receptors (NLRs), T cell cytokines, and transcription factors in lung tissue were examined. Different mRNA expression profiles of TLRs, NLRs, T cell cytokines, and transcription factors were observed. In the mild model, Il10 showed the largest increase in expression, whereas in the severe model, it was Inf γ with the largest increase. Expression of Tbet was also significantly increased in the severe model. Inflammation and immunity are differentially regulated in mild and severe experimental asthma. This preclinical data may help in directing clinical research towards a better understanding and therapy in mild and severe asthmatic patients.

IL-10 and IL-17F Promoter Single Nucleotide Polymorphism and Asthma: A Case-Control Study in South India

“…Unlike this study, most of the studies on IL-10 SNPs and IgE immunoglobulin E, SE standard error of mean, FVC forced vital capacity, FEV1 forced expiratory volume in 1 s, PEF peak expiratory flow Lung asthma have not assessed the association of IL-10 SNPs with different subgroups of asthma severity (GINA), possibly containing a heterogeneous severity groups. Reports suggest different pathogenesis mechanisms, pathways, and cytokine profiles in mild as compared to severe asthma [38]. There is a need for further analysis of our subjects with different asthma severities to understand the pathogenetic mechanism of IL-10 in mild asthma.…”

The Combination Therapy of Dietary Galacto-Oligosaccharides With Budesonide Reduces Pulmonary Th2 Driving Mediators and Mast Cell Degranulation in a Murine Model of House Dust Mite Induced Asthma

“…For differential BAL cell counts, cytospin preparations were made and stained with Diff-Quick (Merz and Dade A.G., Düdingen, Switzerland). Numbers of lymphocytes, eosinophils, macrophages and neutrophils were scored with light microscopy ( 28 ). Afterwards the lavage the right lung was used to prepare lung homogenates, while half of the left lung was used for flowcytometry and the other half of the left lung for in vitro re-stimulation.…”

Regulatory T Cell Depletion Abolishes the Protective Effect of Dietary Galacto-Oligosaccharides on Eosinophilic Airway Inflammation in House Dust Mite–Induced Asthma in Mice

“…For differential BALF cell counts, cytospin preparations were stained with Diff-Quik (Merz & Dade A.G.). Numbers of eosinophils, lymphocytes, and neutrophils were scored with light microscopy (25).…”