IL‐13 enhances agonist‐evoked calcium signals and contractile responses in airway smooth muscle

Abstract

Growing evidence suggests that interleukin (IL)-13, a Th2-type cytokine, plays a critical role in the development of bronchial hyper-responsiveness (BHR), an essential feature of asthma, although the underlying mechanisms remain unknown. In the present study, we investigated whether IL-13 directly affects airway smooth muscle (ASM) function. In murine tracheal rings, IL-13 (100 ng ml À1 , 24 h) significantly increased both the carbachol-and KCl-induced maximal force generation without affecting ASM sensitivity. In cultured human ASM cells, IL-13 (50 ng ml À1 , 24 h) also augmented cytosolic calcium levels to bradykinin, histamine and carbachol by 60, 35 and 26%, respectively. The present study demonstrates that IL-13 may promote BHR by directly modulating ASM contractility, an effect that may be due to enhanced G protein-coupled receptor (GPCR)-associated calcium signaling.

The Association of Cortactin with Profilin-1 Is Critical for Smooth Muscle Contraction

“…IL-13 has been implicated in the hyperactivity of airway smooth muscle (49). In addition, increases in intracellular Ca 2ϩ signaling may also contribute to the pathogenesis of smooth muscle hyperreactivity (50).…”

Bitter Taste Receptor Function in Asthmatic and Nonasthmatic Human Airway Smooth Muscle Cells

“…Activation of the EP1 part of the dimer by PGE 2 in an inflammatory environment causes a decrease in b 2 AR function due to its uncoupling from Gs (27). IL-13 and TNF-a also decrease b-agonist functional responses in PCLSs and increase contractile responses to agonists acting at procontractile GPCRs (28)(29)(30)(31). Even in passaged cultured HASM cells, without the addition of proinflammatory agents in the media, cells derived from patients with fatal asthma show distinct phenotypes compared with cells derived from donors without asthma.…”

Modulation of ozone-induced airway hyperresponsiveness and inflammation by interleukin-13

“…Similarly, the effect of IL-13 in increasing AHR may be through a direct action on the ASM, since IL-13 has been shown to directly increase ASM contractility through the activation of IL-13 receptors identified on ASM cells [31]. IL-13 increases carbachol-and KCl-induced maximal force of murine tracheal rings [32]. IL-13 also reduces isoproterenol-induced relaxation as measured by cell stiffness in human ASM cells [31].…”