Cysteinyl leukotriene upregulates IL-11 expression in allergic airway disease of mice

Abstract

Chronic airway inflammation and airway remodeling are important features of bronchial asthma. IL-11 is one of the important mediators involved in the process of airway inflammation and remodeling. Cysteinyl leukotrienes (cysLTs) play roles in recruitment of inflammatory cells, airway smooth muscle contraction, vascular leakage, increased mucus secretion, decreased mucociliary clearance, and airway fibrosis. An aim of the present study was to determine the effect of the cysLTs on the regulation of IL-11 expression. We used a C57BL/6 mouse model of allergic airway disease and murine tracheal epithelial cells to examine the effects of cysLTs on the regulation of IL-11 expression. Our present study with an ovalbumin-induced murine model of allergic airway disease revealed that levels of leukotriene C(4) (LTC(4)) in bronchoalveolar lavage fluids were increased and that administration of montelukast or pranlukast reduced the increased levels of LTC(4); the increased expression of IL-11 protein and mRNA in lung tissues; airway inflammation, bronchial hyperresponsiveness; the increased levels of TGF-beta(1), IL-4, and IL-13 in bronchoalveolar lavage fluids and lung tissues; and airway fibrosis. In addition, LTC(4) stimulates epithelial cells to produce IL-11. Our results also showed that cysLT type 1 receptor antagonists downregulated the activity of a transcription factor, nuclear factor kappaB, and BAY 11-7085 substantially reduced the increased levels of IL-11 after ovalbumin inhalation. These results suggest that cysLTs regulate the IL-11 expression in allergic airway disease. These findings provide one of the molecular mechanisms for the effects of cysLTs on airway inflammation and fibrosis in allergic airway diseases.