Abstract

Introduction:

Asthma is a chronic inflammatory disorder of the airways in which many cells and cellular elements play a role, especially mast cells, eosinophils, T lymphocytes, macrophages, neutrophils, and epithelial cells. This study investigated the role of Wnt5a signals in the development of allergic asthma.

Method:

A murine ovalbumin (OVA)-induced allergic asthma model was used. After OVA sensitisation using two injections of OVA in Wnt5aflox/flox iSma Cre Tomato mice and Wnt5aWildtype iSma Cre Tomato mice.  Tamoxifen dependent Cre-Lox system was used to induce Wnt5a knock out in alphaSMA expressing cells. To induce allergic asthma, sensitized mice were challenged by OVA inhalation. Control groups were only treated with tamoxifen, but no asthma was induced. After 5 weeks, lung function was measured, BAL fluid collected and serum removed; animals were then sacrificed and the organs removed for further rtPCR, ELISA and histological and immune-histological investigations.

Results:

Between Wnt5aKO and iSmaCre asthma groups eosinophilic reaction and a deterioration in lung function measurements were seen in Wnt5a knockout mice. In addition, levels of various cytokines such as interleukin (IL)-4, IL-11, IL-13, and interferon-gamma were significantly increased in the Wnt5a knockout experimental group. Increased collagen, alpha smooth muscle cell hypertrophy and increased goblet cells was seen in histological and immune-histological investigations.

Discussion:

Our results show that Wnt5a expression in smooth muscle cells and myofibroblasts attenuated the development and progression of allergic asthma, but more studies are needed to determine the molecular mechanisms of Wnt5a in the development of allergic asthma.