Abstract
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.
Highlights
Pendrin (SLC26A4) is an electroneutral anion exchanger, transporting iodide, bicarbonate, hydroxide, thiocyanate, and formate for chloride [1]
The exchanger was shown to be upregulated in airway epithelial cells following stimulation with allergic cytokines such as IL-13, IL-4, and IL-17, in asthma or chronic obstructive pulmonary disease (COPD) mouse models and in patients with asthma, cystic fibrosis (CF), rhinovirus infections, rhinitis, chronic rhinosinusitis, and pertussis infection [19,20,21,30,88,89,90,91,92,93]., In particular, the pathogenesis and disease severity of asthma, allergic rhinitis, and chronic sinusitis with nasal polyps are driven by the activation of eosinophils and CD4+ cells, leading to a Th2 cytokine response which mainly includes IL-4 and IL-13 release [42,94,95]
We provided a description of the IL-mediated pendrin transcriptional regulation and the consequent dysregulation of various molecular mechanisms during inflammatory response in airway and esophageal epithelia
Summary
Pendrin (SLC26A4) is an electroneutral anion exchanger, transporting iodide, bicarbonate, hydroxide, thiocyanate, and formate for chloride [1]. It is a 780-amino-acid-long highly hydrophobic glycoprotein [2], with three putative extracellular glycosylation sites [3,4]. Pendrin mediates Cl−/HCO3− exchange in order to control the acid–base balance of the endolymph, an essential requisite for a normal hearing [9,10,11]. Attention is focused on interleukin-mediated transcriptional regulation of pendrin in bronchial and esophageal epithelia, its effects on the physiology of these two tissues, and the relationship with the etiology of particular diseases
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