WNK Inhibition Increases Surface Liquid pH and Host Defense in Cystic Fibrosis Airway Epithelia

welcome to Red in motion, our video will discuss an important article in the American Journal of respiratory cell and molecular biology. Here we discuss Wnk

inhibition

, increased

surface

fluid pH, and

host

defense

in

cystic

fibrosis

. Airway

epithelia

by researchers at the University of Iowa and the University. of Buffalo Cystic Fibrosis CF is characterized by impaired electrolyte transport that results in inflammation of the lung tissue. Reduced secretion of bicarbonate ions leads to acidification of the

airway

surface

. Liquid ASL, which disrupts

host

defense

s in CF patients, may help understand the mechanisms that control the aslf phase. identify novel therapeutic targets for CF wnk kinases governed by carbonate and chloride ion transport in various

epithelia

l tissues; however, their functions in

airway

epithelia are not well understood.

The researchers sought to examine whether phasl was regulated by wnk kinases in CF using primary cultures of differentiated human airway epithelia. Cells The study identified two isoforms of wnk kinase, wnk1 and wnk2, expressed in airway cells that were involved in anion secretion. Pharmacological

inhibition

of wnk kinase significantly increased CF and non-cfph ASL in differentiated primary epithelial cells and ameliorated host insults that are otherwise suppressed in CF. the increase in PH was dependent on the bicarbonate ion and was linked to the downstream proteins spak and osr1, which markedly inhibited the expression of wnk1 or wnk2. Led to an increase in cfphasl.

Inhibition of wnk also led to a decrease in chloride ion secretion and response to bumetanide, an electrolyte. interestingly transporter inhibitor fumetonide alone or basolateral substitution of the alkalinized cffasl chloride ion these findings show that the balance between transepithelial chloride ion and bicarbonate secretion is influenced by wnk kinases. Wnk kinase inhibitors. Therefore, they may serve as potential therapies for CF, furthermore, vasolateral chloride ion reduction may increase phase. and improve host defenses in CF patients. For more details, read the article by Dr. Tayab Rahman and his colleagues touching red in motion.