The Role of Pendrin in the Airways: Links with Asthma and COPD

Izuhara, Kenji; Suzuki, Shingo; Nofziger, Charity; Ogawa, Masahiro; Nanri, Yasuhiro; Mitamura, Yasutaka; Yoshihara, Tomohito; Pedemonte, Nicoletta; Galietta, Luis J. V.; Paulmichl, Markus

doi:10.1007/978-3-319-43287-8_9

Cited by 2 publications

(3 citation statements)

References 69 publications

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“…In the bronchial epithelium, a fundamental role is attributed to the ASL, a thin fluidic layer whose composition and thickness is regulated by several transporters and ion channels, aquaporin (AQP) water channels, salt-sensitive enzymes, and peptide antibiotics [96]. Interestingly, many of these entities deputed to ASL regulation are altered by IL-4 and IL-13 [114]. Both cytokines increase the expression and activity of calcium-activated chloride channels (CaCCs) and the cystic fibrosis transmembrane conductance regulator (CFTR) [18,115,116,117,118], but downregulate the epithelial sodium channel (EnaC) [117].…”

Section: Pendrin In the Airwaysmentioning

confidence: 99%

Interleukin-Mediated Pendrin Transcriptional Regulation in Airway and Esophageal Epithelia

Vanoni¹,

Scantamburlo²,

Dossena

et al. 2019

IJMS

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Pendrin (SLC26A4), a Cl−/anion exchanger, is expressed at high levels in kidney, thyroid, and inner ear epithelia, where it has an essential role in bicarbonate secretion/chloride reabsorption, iodide accumulation, and endolymph ion balance, respectively. Pendrin is expressed at lower levels in other tissues, such as airways and esophageal epithelia, where it is transcriptionally regulated by the inflammatory cytokines interleukin (IL)-4 and IL-13 through a signal transducer and activator of transcription 6 (STAT6)-mediated pathway. In the airway epithelium, increased pendrin expression during inflammatory diseases leads to imbalances in airway surface liquid thickness and mucin release, while, in the esophageal epithelium, dysregulated pendrin expression is supposed to impact the intracellular pH regulation system. In this review, we discuss some of the recent findings on interleukin-mediated transcriptional regulation of pendrin and how this dysregulation impacts airway and esophagus epithelial homeostasis during inflammatory diseases.

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Section: Pendrin In the Airwaysmentioning

confidence: 99%

Interleukin-Mediated Pendrin Transcriptional Regulation in Airway and Esophageal Epithelia

Vanoni¹,

Scantamburlo²,

Dossena

et al. 2019

IJMS

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“…Airway surfaces are covered by a thin layer of fluid, ASL, whose composition and volume are critical to ensure proper mucociliary clearance and maintain innate defense systems [ 6 ]. The amount and composition of ASL are regulated by the balance between fluid secretion and absorption coordinated by several ion channels and transporters, including pendrin.…”

Section: The Role Of Pendrin In Airway Surface Liquid (Asl)mentioning

confidence: 99%

“…It has been sporadically reported that IL-4 and/or IL-13, signature type 2 cytokines, influence anion transport in airway tissues [ 6 ]. However, the underlying mechanism of how anion transport in airway tissues leads to inflammation has not been sufficiently explained.…”

Section: Introductionmentioning

confidence: 99%

The Significance of Hypothiocyanite Production via the Pendrin/DUOX/Peroxidase Pathway in the Pathogenesis of Asthma

Izuhara

Suzuki

Ogawa

et al. 2017

Oxidative Medicine and Cellular Longevity

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Inhaled corticosteroids (ICSs) are used as first-line drugs for asthma, and various novel antiasthma drugs targeting type 2 immune mediators are now under development. However, molecularly targeted drugs are expensive, creating an economic burden on patients. We and others previously found pendrin/SLC26A4 as a downstream molecule of IL-13, a signature type 2 cytokine critical for asthma, and showed its significance in the pathogenesis of asthma using model mice. However, the molecular mechanism of how pendrin causes airway inflammation remained elusive. We have recently demonstrated that hypothiocyanite (OSCN−) produced by the pendrin/DUOX/peroxidase pathway has the potential to cause airway inflammation. Pendrin transports thiocyanate (SCN−) into pulmonary lumens at the apical side. Peroxidases catalyze SCN− and H2O2 generated by DUOX into OSCN−. Low doses of OSCN− activate NF-κB in airway epithelial cells, whereas OSCN− in high doses causes necrosis of the cells, inducing the release of IL-33 and accelerating inflammation. OSCN− production is augmented in asthma model mice and possibly in some asthma patients. Heme peroxidase inhibitors, widely used as antithyroid agents, diminish asthma-like phenotypes in mice, indicating the significance of this pathway. These findings suggest the possibility of repositioning antithyroid agents as antiasthma drugs.

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The Role of Pendrin in the Airways: Links with Asthma and COPD

Cited by 2 publications

References 69 publications

Interleukin-Mediated Pendrin Transcriptional Regulation in Airway and Esophageal Epithelia

Interleukin-Mediated Pendrin Transcriptional Regulation in Airway and Esophageal Epithelia

The Significance of Hypothiocyanite Production via the Pendrin/DUOX/Peroxidase Pathway in the Pathogenesis of Asthma

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