Journal article
TNF alpha and IL-17 alkalinize airway surface liquid through CFTR and pendrin
American Journal of Physiology: Cell Physiology, Vol.319(2), pp.C331-C344
08/01/2020
DOI: 10.1152/ajpcell.00112.2020
PMCID: PMC7500220
PMID: 32432926
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 (pH(ASL)). Neutrophil-predominant inflammation is a hallmark of several airway diseases, and TNF alpha and IL-17 are key drivers. However, how these cytokines perturb pH(ASL) regulation is uncertain. In primary cultures of differentiated human airway epithelia, TNFa decreased and IL-17 did not change pH(ASL). However, the combination (TNF alpha+EL-17) markedly increased pH(ASL) by increasing HCO3- secretion. TNF alpha+IL-17 increased expression and function of two apical HCO3- transporters, CI-1R anion channels and pendrin Cl-/HCO3- exchangers. Both were required for maximal alkalinization. TNF alpha+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 TNF alpha +IL-17 stimulate HCO3 secretion via CFTR and pendrin to alkalinize ASL, which may represent an important defense mechanism in inflamed airways.
Details
- Title: Subtitle
- TNF alpha and IL-17 alkalinize airway surface liquid through CFTR and pendrin
- Creators
- Tayyab Rehman - Roy J. and Lucille A. Carver College of MedicineIan M. Thornell - Roy J. and Lucille A. Carver College of MedicineAlejandro A. Pezzulo - Roy J. and Lucille A. Carver College of MedicineAndrew L. Thurman - Roy J. and Lucille A. Carver College of MedicineGuillermo S Romano Ibarra - Roy J. and Lucille A. Carver College of MedicinePhilip H. Karp - Roy J. and Lucille A. Carver College of MedicinePing Tan - Roy J. and Lucille A. Carver College of MedicineMichael E. Duffey - University at Buffalo, State University of New YorkMichael J. Welsh - Roy J. and Lucille A. Carver College of Medicine
- Resource Type
- Journal article
- Publication Details
- American Journal of Physiology: Cell Physiology, Vol.319(2), pp.C331-C344
- DOI
- 10.1152/ajpcell.00112.2020
- PMID
- 32432926
- PMCID
- PMC7500220
- NLM abbreviation
- Am J Physiol Cell Physiol
- ISSN
- 0363-6143
- eISSN
- 1522-1563
- Publisher
- Amer Physiological Soc
- Number of pages
- 14
- Grant note
- Cystic Fibrosis Foundation RDP pilot award Cystic Fibrosis Foundation Research Development Program Gilead Sciences Research Program in Cystic Fibrosis HL007638 / National Institutes of Health; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA HL051670; HL091842 / National Institutes of Health (National Heart, Lung, and Blood Institute); United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Heart Lung & Blood Institute (NHLBI)
- Language
- English
- Date published
- 08/01/2020
- Academic Unit
- Neurology; Molecular Physiology and Biophysics; Pulmonary, Critical Care, and Occupational Medicine; Iowa Neuroscience Institute; Fraternal Order of Eagles Diabetes Research Center; Neurosurgery; Internal Medicine
- Record Identifier
- 9984259506302771
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