House dust mite (HDM) challenge is commonly used in murine models of allergic
asthma for preclinical pathophysiological studies. However, few studies define objective readouts or
biomarkers in this model. In this study we characterized immune responses and defined molecular markers that are specifically altered after HDM challenge. In this murine model, we used repeated HDM challenge for two weeks which induced hallmarks of allergic
asthma seen in humans, including
airway hyper-responsiveness (AHR) and elevated levels of circulating total and HDM-specific
IgE and
IgG1. Kinetic studies showed that at least 24 h after last HDM challenge results in significant AHR along with eosinophil infiltration in the lungs. Histologic assessment of lung revealed increased epithelial thickness and goblet cell
hyperplasia, in the absence of airway wall
collagen deposition, suggesting ongoing tissue repair concomitant with acute allergic
lung inflammation. Thus, this model may be suitable to delineate airway
inflammation processes that precede
airway remodeling and development of fixed
airway obstruction. We observed that a panel of
cytokines e.g. IFN-γ, IL-1β,
IL-4,
IL-5,
IL-6, KC, TNF-α,
IL-13,
IL-33, MDC and TARC were elevated in lung tissue and bronchoalveolar fluid, indicating local
lung inflammation. However, levels of these
cytokines remained unchanged in serum, reflecting lack of systemic
inflammation in this model. Based on these findings, we further monitored the expression of 84 selected genes in lung tissues by quantitative real-time PCR array, and identified 31 mRNAs that were significantly up-regulated in lung tissue from HDM-challenged mice. These included genes associated with human
asthma (e.g. clca3, ear11,
il-13, il-13ra2, il-10, il-21, arg1 and chia1) and leukocyte recruitment in the lungs (e.g. ccl11, ccl12 and ccl24). This study describes a biosignature to enable broad and systematic interrogation of molecular mechanisms and intervention strategies for airway
inflammation pertinent to allergic
asthma that precedes and possibly potentiates
airway remodeling and
fibrosis.