Effect of IL-13 on Serotonin mediated Airway Smooth Muscle Contraction

Abstract: Introduction: Asthma is a disease that occurs worldwide and approximately 300 million people carry this disease. It is characterized by chronic inflammation, airway obstruction and airway hyper-responsiveness (AHR). This T-lymphocyte controlled disease has symptoms such as coughing, wheezing, and chest tightness. In addition to chronic inflammation, asthma is also caused by overproduction of mucus and airway wall remodelling. The chronic inflammation and airway wall remodelling are suggested to contribute to the AHR and airway obstruction. AHR is a way to measure the reactivity in the airways in asthmatics. IL-13 has been shown to play an important role in the development of AHR, and biopsies from bronchial submucosa and air way smooth muscle (ASM) in humans have shown an increased concentration of IL-13 in severe asthma. Aim: The aim of this work was to evaluate if IL-13 is able to enhance the 5-HT response in mouse tracheal segments, which had been cultured for 2 days and, if so, try to unravel the underlying mechanism for this phenomenon. Literature reports that IL-13 enhanced contractions in mouse trachea in presence of KCl and CCH. Earlier work within this project did not find any clear proof for this observation. However, in this work this observation will be evaluated in a more controlled fashion by correcting for size and location of the trachea. Methods: The trachea was removed from Balp/c mice and cultured in small wells for two days in DMEM medium and various additions were performed to the medium for understanding the effect of e.g. IL-13 on the cells. The contractility change due to IL-13 and various additions in segments challenged with KCL, CCH and 5-HT were measured in a tissue-organ bath. Results and Conclusion: A more enhanced CCH induced contraction of IL-13 treated segments was obtained for the lower part compared to the upper part of the trachea. IL-13 enhanced the response in the ASM to 5-HT after two days of culturing. An increased concentration of the cytokine IL-13 in the airways from TH2-cells enhances the reactivity to 5-HT in the ASM. The underlying mechanism might involve JNK and ERK but more experiments are needed to statistically ensure this claim.