The influence of interleukin-13 on force generation in airway smooth muscle tissue

Airway smooth muscle (ASM) has been implicated in the pathophysiology of asthma by contributing to excessive airway narrowing and Airway Hyperresponsiveness (AHR). Inflammation has also been suggested as a mechanism contributing to AHR. Levels of Interleukin-13 (IL-13), an inflammatory mediator, are increased in asthmatic sera and can alter the expression of specific contractile genes/proteins in cultured ASM cells. In cultured cells, IL-13 can cause increased ASM contractility and force generation in response to different contractile agonists such as acetylcholine (ACh), KCl, or histamine. However, there remains a lack of consensus regarding whether IL-13 can induce changes in mechanical properties of ASM tissue in response to all, or only some, contractile agonists. Our objective was to investigate the influence of IL-13 on the force generation of isolated ASM tissue in response to a variety of agonists. Ovine tracheal smooth muscle was isolated, bathed in Krebs solution, and then equilibrated using electrical field stimulation. To obtain baseline mechanical measurements, tissues were either contracted with a range of ACh concentrations, pre-stimulated with ACh then relaxed with progressively increasing doses of isoproterenol (ISO), or contracted with single a single concentration of KCl or histamine (n=5 per condition). Paired samples from each tissue were pinned at in situ length and incubated for 24h or 72h with or without IL-13 in serum-free DMEM. Responses were compared to their baseline measurements after incubation to determine the influence of IL-13. Compared to non-exposed tissues, IL-13 did not increase maximal force or sensitivity to a range of ACh concentrations after 24 or 72h (n=5 each), nor did it impede the relaxation of ASM induced by ISO after 24h (n=5). Likewise, response to KCl was not changed by IL-13 after 72h (n=5). Response to histamine was ~120% higher compared to control (t=72h) after treatment (% of baseline maximal force, n=5, p=0.03). These findings contrast with previous literature in ASM cell culture experiments. In tissue strips, IL-13 did not induce significant changes to ASM mechanics in response to ACh, ISO, or KCl. However, IL-13 did influence histamine-induced contractile response suggesting a potential avenue by which airway inflammation influences ASM contraction.Medicine, Faculty ofPathology and Laboratory Medicine, Department ofGraduat