TNF α and IL-17 Alkalinize Airway Surface Liquid through CFTR and Pendrin.

TNFα and IL-17 Alkalinize Airway Surface Liquid through CFTR and Pendrin. Am J Physiol Cell Physiol. 2020 May 20;: Authors: Rehman T, Thornell IM, Pezzulo AA, Thurman AL, Romano Ibarra GS, Karp PH, Tan P, Duffey ME, Welsh MJ 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 (HCO3¯) 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 HCO3¯ secretion. TNFα+IL-17 increased expression and function of two apical HCO3¯ transporters, CFTR anion channels and pendrin Cl-/HCO3- exchangers. Both were required for maximal alkalinization. TNFα+IL-17 induced pendrin expression primarily in secretory cells where it was co-expressed with CFTR. Interestingly, significant pendrin expression was not detected in CFTR-rich ionocytes. These results indicate that TNFα+IL-17 stimulate HCO3- secretion via CFTR and pendrin to alkalinize ASL, which may represent an important defense mechanism in inflamed airways. ...
Source: Am J Physiol Cell Ph... - Category: Cytology Authors: Tags: Am J Physiol Cell Physiol Source Type: research