The effect of IL-13 and IL-13R130Q, a naturally occurring IL-13 polymorphism, on the gene expression of human airway smooth muscle cells

Syed, Farhat; Panettieri, Reynold A.; Tliba, Omar; Huang, Chris; Li, Katherine; Bracht, Michelle; Amegadzie, Bernard Y.; Griswold, Don E.; Li, Li; Amrani, Yassine

doi:10.1186/1465-9921-6-9

Cited by 35 publications

(29 citation statements)

References 30 publications

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“…A number of reports have shown that IL-13 may exert its deleterious effects in asthma by acting directly on resident airway cells, including epithelial cells and airway smooth muscle cells (Kuperman et al, 2002;Tliba et al, 2003;Syed et al, 2005). Our study supports and extends these findings.…”

Section: Discussionsupporting

confidence: 82%

Interleukin 13 Increases Contractility of Murine Tracheal Smooth Muscle by a Phosphoinositide 3-kinase p110δ-Dependent Mechanism

et al. 2008

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The Th2 cytokine interleukin (IL) 13 can elicit a number of responses consistent with a key role in the pathogenesis of asthma. We have used pharmacological and genetic approaches to demonstrate the role of signaling via the class I phosphoinositide 3-kinase p110␦ isoform in IL-13-induced hyper-responsiveness of murine tracheal smooth muscle contractility in vitro. IL-13 treatment of tracheal tissue is associated with an early activation of phosphoinositide 3-kinase (PI3K), as assessed by phosphorylation of Akt. Tracheal smooth muscle contractility is enhanced by overnight incubation with IL-13, resulting in increased maximal contractions (E max ) to carbachol (CCh) and KCl. Inhibition of PI3K by the non-isoform-selective inhibitors wortmannin or 2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one (LY294002), or the selective inhibitor of the PI3K p110␦ isoform 2-(6-aminopurin-9-ylmethyl)-5-methyl-3-O-tolyl-3H-quinazolin-4-one (IC87114), prevented IL-13-induced hyper-responsiveness. Consistent with a role for PI3K p110␦ in IL-13-induced hyper-responsiveness, IL-13 was unable to induce hyper-responsiveness in tissues from mice expressing the catalytically inactive form of p110␦ (p110␦ D910A ). These data indicate that IL-13 contributes to tracheal smooth muscle hyper-responsiveness via the PI3K p110␦ isoform. In addition to previously reported effects on airway inflammation, inhibition of PI3K p110␦ may be a useful target for the treatment of asthma by preventing IL-13-induced airway smooth muscle hyper-responsiveness.

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Section: Discussionsupporting

confidence: 82%

Interleukin 13 Increases Contractility of Murine Tracheal Smooth Muscle by a Phosphoinositide 3-kinase p110δ-Dependent Mechanism

et al. 2008

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“…Our findings indicate that IL-33 regulates the expression of these genes through an IL-13-dependent pathway. IL-13 has been shown to directly modulate expression of collagen VIa, collagen III, and TIMP-1 in previous studies (44,45). Interestingly, fibronectin-1 expression was increased independently of IL-13 in IL-33-injected skin samples, suggesting that expression of some ECM components may be regulated directly through IL-33-or other IL-13-independent downstream mediators.…”

Section: Discussionmentioning

confidence: 80%

IL-33 Induces IL-13–Dependent Cutaneous Fibrosis

Rankin¹,

Mumm²,

Murphy³

et al. 2009

The Journal of Immunology

198

156

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IL-33 is constitutively expressed in epithelial barrier tissues, such as skin. Although increased expression of IL-33/IL-33R has been correlated with fibrotic disorders, such as scleroderma and progressive systemic sclerosis, the direct consequences of IL-33 release in skin has not been reported. To determine the effects of dysregulated IL-33 signaling in skin, we administered IL-33 s.c. and monitored its effects at the injection site. Administration of IL-33 resulted in IL-33R–dependent accumulation of eosinophils, CD3+ lymphocytes, F4/80+ mononuclear cells, increased expression of IL-13 mRNA, and the development of cutaneous fibrosis. Consistent with extensive cutaneous tissue remodeling, IL-33 resulted in significant modulation of a number of extracellular matrix-associated genes, including collagen VI, collagen III, and tissue inhibitor of metalloproteases-1. We establish that IL-33–induced fibrosis requires IL-13 using IL-13 knockout mice and eosinophils using ΔdblGATA mice. We show that bone marrow-derived eosinophils secrete IL-13 in response to IL-33 stimulation, suggesting that eosinophil-derived IL-13 may promote IL-33–induced cutaneous fibrosis. Collectively, our results identify IL-33 as a previously unrecognized profibrotic mediator in skin and highlight the cellular and molecular pathways by which this pathology develops.

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“…Jarai et al investigated the H 1 receptor expression in cultured ASM in response to IL-13 and found that there was a 2.6-fold increase in its gene expression after 4 h (Jarai et al 2004). More recently, Syed et al found that the mRNA expression of the H 1 receptor in cultured ASM was increased 1.3-fold in response to stimulation with IL-13 (50 ng/mL) (Syed et al 2005). Taken together, these studies suggest that IL-13, a central inflammatory cytokine in asthma, can upregulate expression of the histamine H 1 receptor in ASM, likely leading to augmented intracellular calcium release and ASM contractility in response to histamine.…”

Section: Histamine H 1 Receptormentioning

confidence: 69%

Gene expression in asthmatic airway smooth muscle: a mixed bag

Pascoe

Swyngedouw

Seow

et al. 2015

Can. J. Physiol. Pharmacol.

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It has long been known that airway smooth muscle (ASM) contraction contributes significantly to the reversible airflow obstruction that defines asthma. It has also been postulated that phenotypic changes in ASM contribute to the airway hyperresponsiveness (AHR) that is a characteristic feature of asthma. Although there is agreement that the mass of ASM surrounding the airways is significantly increased in asthmatic compared with non-asthmatic airways, it is still uncertain whether there are quantitative or qualitative changes in the level of expression of the genes and proteins involved in the canonical contractile pathway in ASM that could account for AHR. This review will summarize past attempts at quantifying gene expression changes in the ASM of asthmatic lungs as well as non-asthmatic ASM cells stimulated with various inflammatory cytokines. The lack of consistent findings in asthmatic samples coupled with the relative concordance of results from stimulated ASM cells suggests that changes to the contractility of ASM tissues in asthma may be dependent on the presence of an inflammatory environment surrounding the ASM layer. Removal of the ASM from this environment could explain why hypercontractility is rarely seen ex vivo.Key words: asthma, airway smooth muscle, gene expression, protein expression, cytokines. Résumé :On sait depuis longtemps que la contraction du muscle lisse respiratoire (MLR) contribue de manière significative à l'obstruction réversible du débit d'air qui définit l'asthme. Il a aussi été postulé que des changements phénotypiques dans le MLR contribue à l'hyperréactivité bronchique (HRB) qui caractérise l'asthme. Même si l'on s'accorde sur le fait que la masse de MLR qui entoure les voies respiratoires est significativement plus importante en situation d'asthme comparativement à l'absence d'asthme, on ne sait pas encore avec certitude si des changements quantitatifs ou qualitatifs du niveau d'expression de gènes et de protéines impliqués dans les voies standards de régulation de la contraction chez le MLR pourraient expliquer l'HRB. Cet article de revue résumera les tentatives passées de quantification de changements d'expression génique dans des cellules de MLR de poumons asthmatiques et non asthmatiques, stimulées à l'aide de différentes cytokines inflammatoires. L'absence de données cohérentes issues d'échantillons asthmatiques, couplée à la concordance relative des résultats obtenus à partir de cellules de MLR stimulées suggère que les changements de contractilité du MLR dans l'asthme peuvent être dépendants de la présence d'un environnement inflammatoire autour de la couche de MLR. Le fait de retirer le MLR de son environnement pourrait expliquer pourquoi l'hyper-contractilité est rarement observée ex vivo. [Traduit par la Rédaction] Mots-clés : asthme, muscle lisse respiratoire, expression génique, expression protéique, cytokines.

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The effect of IL-13 and IL-13R130Q, a naturally occurring IL-13 polymorphism, on the gene expression of human airway smooth muscle cells

Abstract: The data supports the hypothesis that gene modulation by IL-13 in ASM may be essential for the events leading to the development of allergic asthma.

Cited by 35 publications

References 30 publications

Interleukin 13 Increases Contractility of Murine Tracheal Smooth Muscle by a Phosphoinositide 3-kinase p110δ-Dependent Mechanism

Interleukin 13 Increases Contractility of Murine Tracheal Smooth Muscle by a Phosphoinositide 3-kinase p110δ-Dependent Mechanism

IL-33 Induces IL-13–Dependent Cutaneous Fibrosis

Gene expression in asthmatic airway smooth muscle: a mixed bag

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