Title: TNFα and IL-17 alkalinize airway surface liquid through CFTR and pendrin.

Authors: Rehman, Tayyab; Thornell, Ian M; Pezzulo, Alejandro A; Thurman, Andrew L; Romano Ibarra, Guillermo S; Karp, Philip H; Tan, Ping; Duffey, Michael E; Welsh, Michael J

Published In Am J Physiol Cell Physiol, (2020 08 01)

Abstract: The pH of airway surface liquid (ASL) is a key factor that determines respiratory host defense; ASL acidification impairs and alkalinization enhances key defense mechanisms. Under healthy conditions, airway epithelia secrete base ([Formula: see text]) and acid (H+) to control ASL pH (pHASL). Neutrophil-predominant inflammation is a hallmark of several airway diseases, and TNFα and IL-17 are key drivers. However, how these cytokines perturb pHASL regulation is uncertain. In primary cultures of differentiated human airway epithelia, TNFα decreased and IL-17 did not change pHASL. However, the combination (TNFα+IL-17) markedly increased pHASL by increasing [Formula: see text] secretion. TNFα+IL-17 increased expression and function of two apical [Formula: see text] transporters, CFTR anion channels and pendrin Cl-/[Formula: see text] exchangers. Both were required for maximal alkalinization. TNFα+IL-17 induced pendrin expression primarily in secretory cells where it was coexpressed with CFTR. Interestingly, significant pendrin expression was not detected in CFTR-rich ionocytes. These results indicate that TNFα+IL-17 stimulate [Formula: see text] secretion via CFTR and pendrin to alkalinize ASL, which may represent an important defense mechanism in inflamed airways.

PubMed ID: 32432926

MeSH Terms: No MeSH terms associated with this publication