Association of IL-33 in modeling type-2 airway inflammation and pulmonary emphysema in mice

Abstract

We developed pulmonary emphysema and a type 2 airway inflammation overlap mouse model. The bronchoalveolar lavage (BAL) interleukin 13 (IL-13), IL-4, and IL-5 levels in the overlap model were higher than in the pulmonary emphysema model and lower than in the type 2 airway inflammation model, but IL-33 level in the lung was higher than in other models. IL-33 and interferon-γ (IFNγ) in lungs may control the severity of a type 2 airway inflammation in lung.

Keywords: COPD; IFNγ; IL‐13; IL‐33; IL‐4; IL‐5; asthma; innate immunity.

Figure 1

Airway inflammation in mouse models of asthma, emphysema, and asthma–chronic obstructive pulmonary disease overlap (ACO). (A) Protocol for assessing type‐2 airway inflammation (Type‐2), emphysema, and overlap mouse models. (B, C) Pathologies (B) and mean linear intercept (MLI, C) of the mouse lungs (n = 6–8 mice). Bars, 500 μm (×40) and 100 μm (×200). (D) Interleukin 33 (IL‐33) levels in lung lysate. Total, full‐length, and processed IL‐33 (left, middle, and right, respectively) were calculated as described in Figure 1. (E) IL‐4, IL‐5, and IL‐13 levels in bronchoalveolar lavage (BAL) fluid (n = 5–6 mice). (F) Interferon γ (IFNγ), IL‐12, and IL‐27 levels in lung lysate (n = 5–6 mice). Data are pooled from three experiments and expressed as mean ± standard error of the mean (C–F). ****p < .0001, ***p < .001, **p < .01, *p < .05. p values were calculated using one‐way analysis of variance and post hoc Tukey tests (C–F). ALT, Alternaria alternata; PBS, phosphate‐buffered saline; Type‐2, type‐2 airway inflammation; Overlap, type‐2 airway inflammation and pulmonary emphysema overlap.