Upregulation of interleukin-13 receptor chains in bronchial smooth muscle tissues of mouse experimental asthma.

Interleukin-13 (IL-13) is believed to be a central mediator of the induction of airway hyperresponsiveness (AHR), one of the characteristic features of allergic bronchial asthma. The IL-13-mediated events are mainly generated by its binding to functional IL-13 receptor, IL13Ralpha1 chain. In the present study, the changes in the levels of IL-13 receptors in bronchial smooth muscles were determined in mice with AHR induced by antigen inhalation.

Antigen exposure causes activations of signal transducer and activator of transcription 6 (STAT6) and STAT1, but not STAT3, in lungs of sensitized mice.

The signal transducer and activator of transcription (STAT) family of molecules play a critical role in the signaling of many cytokines. In addition to STAT6, implication of STAT1 and STAT3 in the pathogenesis of allergic airway diseases has also been suggested. However, there is little information whether or not antigen challenge to sensitized animals causes the in vivo activation of STAT1 and/or STAT3 in the airways.

Activation of signal transducer and activator of transcription factor 1 by interleukins-13 and -4 in cultured human bronchial smooth muscle cells.

The family of signal transducer and activator of transcription (STAT) factors play a critical role in the signaling of many cytokines. In addition to the involvement of STAT6 in allergic bronchial asthma, both STAT1 and STAT3 have also been implicated. However, there is little information whether or not the T helper 2 cytokines, which cause several key features of allergic asthma, really induce the activation of STAT1 and/or STAT3 in bronchial smooth muscle (BSM) cells.

Phosphorylation of signal transducer and activator of transcription 6 (STAT6) and STAT1, but not STAT3, induced by antigen inhalation in bronchial smooth muscles of sensitized mice.

The signal transducer and activator of transcription (STAT) family of molecules play a critical role in the signaling of many cytokines. In addition to STAT6, implication of STAT1 and STAT3 in the development of airway hyperresponsiveness (AHR) has also been suggested in allergic bronchial asthma. However, there is little information whether or not antigen challenge really causes the in vivo activation of these STAT molecules in bronchial smooth muscles (BSMs).

Interleukin-4 upregulates RhoA protein via an activation of STAT6 in cultured human bronchial smooth muscle cells.

Interleukin-4 (IL-4) is believed to play a role in allergic bronchial asthma, and has been suggested to cause hyperresponsiveness of airway smooth muscle. In the present study, the effects of IL-4 on the expression of RhoA protein, a monomeric GTP-binding protein that contributes to the contraction of smooth muscle, were determined in cultured human bronchial smooth muscle cells (hBSMCs). Incubation of hBSMCs with IL-4 (100ng/mL) caused a distinct phosphorylation of signal transducer and activator of transcription 6 (STAT6), a major signal transducer activated by IL-4, indicating that IL-4 is capable of activating signal transduction in the hBSMCs directly.

A novel STAT6 inhibitor AS1517499 ameliorates antigen-induced bronchial hypercontractility in mice.

Interleukin-13 (IL-13) is one of the central mediators for development of airway hyperresponsiveness in asthma. The signal transducer and activation of transcription 6 (STAT6) is one of the major signal transducers activated by IL-13, and a possible involvement of IL-13/STAT6 pathway in the augmented bronchial smooth muscle (BSM) contraction has been suggested. In the present study, the effect of a novel STAT6 inhibitor, AS1517499, on the development of antigen-induced BSM hyperresponsiveness was investigated.

Interleukin-13 augments bronchial smooth muscle contractility with an up-regulation of RhoA protein.

Interleukin-13 (IL-13) is one of the central mediators for development of airway hyperresponsiveness in asthma. However, its effect on bronchial smooth muscle (BSM) is not well known. Recent studies revealed an involvement of RhoA/Rho-kinase in BSM contraction, and this pathway has now been proposed as a new target for asthma therapy.