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Modulation of Airway Smooth Muscle Contractile Function by TNFα and IL-13 and Airway Hyperresponsiveness in Asthma

  • Yassine AmraniEmail author
Chapter

Abstract

There is no doubt that airway smooth muscle (ASM) is a key player in asthma pathophysiology, as demonstrated by its heightened sensitivity to both direct and indirect contractile stimuli, which leads to exaggerated airway narrowing and airflow obstruction. The therapeutic benefit in severe asthmatics provided by bronchial thermoplasty, a therapy that attenuates bronchoconstriction via reduction of ASM mass, has provided additional support for the concept that ASM function could be abnormally contracting in asthma. The mechanisms in ASM leading to this exaggerated sensitivity to G-protein-coupled receptor (GPCR) agonists, known as bronchial hyper-responsiveness, are still unknown. A number of studies, however, have demonstrated that a direct action of two key pro-asthmatic cytokines, TNFα and IL-13 on ASM, leads to exaggerated ASM contractility via the modulation of GPCR-associated calcium signalling. This chapter reviews the evidence demonstrating a role of both TNFα and IL-13 in driving airway hyperresponsiveness at three different levels: in experimental animal models of asthma, in isolated airway preparations and in isolated ASM cells.

Keywords

Cytokines Calcium metabolism G-protein-coupled receptor Rho pathway Allergen challenge 

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Copyright information

© Springer International Publishing Switzerland 2014

Authors and Affiliations

  1. 1.Department of Infection, Immunity and InflammationUniversity of LeicesterLeicesterUK
  2. 2.Department of Respiratory MedicineInstitute for Lung HealthLeicesterUK

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