Interleukin-13 enhanced Ca2+ oscillations in airway smooth muscle cells

Matsumoto, Hisako; Hirata, Yutaka; Otsuka, Kojiro; Iwata, Toshiyuki; Inazumi, Aya; Ito, Isao; Ogawa, Emiko; Muro, Shigeo; Sakai, Hiroaki; Chin, Kazuo; Oku, Yoshitaka; Mishima, Michiaki

doi:10.1016/j.cyto.2011.10.014

Cited by 26 publications

(11 citation statements)

References 27 publications

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“…In vitro studies, using airway smooth muscle cells of humans and rodents, have shown that IL-13 increases the contractility of smooth muscle, via enhancing Ca 2+ oscillations of airway smooth muscle cells, thus implying a direct stimulatory effect of IL-13 on airway smooth cells [28–30]. In addition, IL-13 was shown to increase the affinity of smooth muscle for acetylcholine released from cholinergic nerves [31].…”

Section: Discussionmentioning

confidence: 99%

IL-13 is a central mediator of chemical-induced airway hyperreactivity in mice

et al. 2017

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BackgroundWhile the importance of the Th2 cytokine IL-13 as a central mediator of airway hyperreactivity (AHR) has been described in allergic protein-induced asthma, this has never been investigated in chemical-induced asthma.ObjectiveWe examined the importance of IL-13 in a mouse model of chemical-induced AHR, using toluene-2,4-diisocyanate (TDI).MethodsIn a first set-up, wild type (WT) and IL-13 knockout (KO) C57Bl/6 mice were dermally treated on days 1 and 8 with 1% TDI or vehicle (acetone/olive oil) on both ears. On day 15, mice received an intranasal instillation with 0.1% TDI or vehicle. In a second set-up, WT mice sensitized with 1% TDI or vehicle, received i.v. either anti-IL-13 or control antibody prior to the intranasal challenge.ResultsTDI-sensitized and TDI-challenged WT mice showed AHR to methacholine, in contrast to TDI-sensitized and TDI-challenged IL-13 KO mice, which also showed lower levels of total serum IgE. TDI-sensitized and TDI-challenged IL-13 KO mice had lower numbers of T-cells in the auricular lymph nodes. TDI-treated WT mice, receiving anti-IL-13, showed no AHR, in contrast to those receiving control antibody, despite increased levels of IgE. Anti-IL-13 treatment in TDI-treated WT mice resulted in lower levels of serum IL-13, but did not induce changes in T- and B-cell numbers, and in the cytokine production profile.Conclusion and clinical relevanceWe conclude that IL-13 plays a critical role in the effector phase of chemical-induced, immune-mediated AHR. This implicates that anti-IL-13 treatment could have a beneficial effect in patients with this asthma phenotype.

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Section: Discussionmentioning

confidence: 99%

IL-13 is a central mediator of chemical-induced airway hyperreactivity in mice

et al. 2017

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“…Ca 2+ influx via SOC channels contributes to PDGFinduced cell migration of airway smooth muscle [166], and increasing [Ca 2+ ] i via other mechanisms also causes substance P-induced cell migration of airway smooth muscle [167] ( Figure 5). Since IL-13 enhances Ca 2+ oscillation in airway smooth muscle cells, cell migration induced by IL-13 may be regulated by Ca 2+ dynamics [168].…”

Section: Cell Migrationmentioning

confidence: 99%

Ca2+ Dynamics and Ca2+ Sensitization in the Regulation of Airway Smooth Muscle Tone

Kumakura¹

2015

Muscle Cell and Tissue

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“…These cytokines play pivotal roles in the pathogenesis of AHR. For example, IL-13 enhances calcium oscillation in airway smooth muscle, and inhibition of IL-13 completely blocks airway hyperreactivity in mouse asthma models (2,7). IL-5 is a key factor for eosinophilia and could therefore be responsible for some of the tissue damage seen in chronic asthma (3).…”

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confidence: 99%

Dissociation of FK506-Binding Protein 12.6 kD from Ryanodine Receptor in Bronchial Smooth Muscle Cells in Airway Hyperresponsiveness in Asthma

Du¹,

Zhao²,

Li³

et al. 2014

Am J Respir Cell Mol Biol

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Airway hyperresponsiveness (AHR) in asthma is predominantly caused by increased sensitivity of bronchial smooth muscle cells (BSMCs) to stimuli. The sarcoplasmic reticulum (SR)-Ca 21 release channel, known as ryanodine receptor (RyR), mediates the contractive response of BSMCs to stimuli. FK506-binding protein 12.6 kD (FKBP12.6) stabilizes the RyR2 channel in a closed state. However, the interaction of FKBP12.6 with RyR2 in AHR remains unknown. This study examined the interaction of FKBP12.6 with RyR2 in BSMCs in AHR of asthma. The interaction of FKBP12.6 with RyR2 and FKBP12.6 expression was determined in a rat asthma model and in BSMCs treated with inflammatory cytokines. The calcium responses to contractile agonists were determined in BSMCs with overexpression and knockdown of FKBP12.6. Asthmatic serum, IL-5, IL-13, and TNF-a enhance the calcium response of BSMCs to contractile agonists and cause dissociation of FKBP12.6 from RyR2 and a decrease in FKBP12.6 gene expression in BSMCs in culture and in ovalbumin (OVA)-sensitized and -challenged rats. Knockdown of FKBP12.6 in BSMCs causes a decrease in the association of RyR2 with FKBP12.6 and an increase in the calcium response of BSMCs. Overexpression of FKBP12.6 increases the association of FKBP12.6 with RyR2, decreases the calcium response of BSMCs, and normalizes airway responsiveness in OVA-sensitized and -challenged rats. Dissociation of FKBP12.6 from RyR2 in BSMCs is responsible for the increased calcium response contributing to AHR in asthma. Manipulating the interaction of FKBP12.6 with RyR2 might be a novel and useful treatment for asthma.Keywords: asthma; airway hyperresponsiveness; calcium; RyR2; FKBP12.6 Clinical RelevanceAlthough enhanced calcium response of bronchial smooth muscle to stimuli has been reported to be involved in asthmatic airway hyperresponsiveness, an interaction of FKBP12.6 with RyR2 on sarcoplasmic reticulum in asthmatic airway hyperresponsiveness has not been investigated. We have shown that increased responsiveness of bronchial smooth muscle in asthma is attributed to the dissociation of FKBP12.6 from ryanodine receptor 2, which promotes calcium release from the sarcoplasmic reticulum.

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Interleukin-13 enhanced Ca2+ oscillations in airway smooth muscle cells

Cited by 26 publications

References 27 publications

IL-13 is a central mediator of chemical-induced airway hyperreactivity in mice

IL-13 is a central mediator of chemical-induced airway hyperreactivity in mice

Ca2+ Dynamics and Ca2+ Sensitization in the Regulation of Airway Smooth Muscle Tone

Dissociation of FK506-Binding Protein 12.6 kD from Ryanodine Receptor in Bronchial Smooth Muscle Cells in Airway Hyperresponsiveness in Asthma

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