The influence of interleukin-13 on force generation in airway smooth muscle tissue
| Autor: | Swyngedouw, Nicholas Eric |
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| Jazyk: | angličtina |
| Rok vydání: | 2016 |
| Druh dokumentu: | Text |
| Popis: | 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 of Pathology and Laboratory Medicine, Department of Graduate |
| Databáze: | Networked Digital Library of Theses & Dissertations |
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