Klotho Inhibits Interleukin-8 Secretion from Cystic Fibrosis Airway Epithelia

Stefanie Krick, Nathalie Baumlin, Sheyla Paredes Aller, Carolina Aguiar, Alexander Grabner, Juliette Sailland, Eliana Mendes, Andreas Schmid, Lixin Qi, Nicolae V. David, Patrick Geraghty, Gwendalyn King, Susan E. Birket, Steven M. Rowe, Christian Faul, Matthias Salathe

Research output: Contribution to journalArticle

15 Scopus citations

Abstract

Chronic inflammation is a hallmark of cystic fibrosis (CF) and associated with increased production of transforming growth factor (TGF) β and interleukin (IL)-8. α-klotho (KL), a transmembrane or soluble protein, functions as a co-receptor for Fibroblast Growth Factor (FGF) 23, a known pro-inflammatory, prognostic marker in chronic kidney disease. KL is downregulated in airways from COPD patients. We hypothesized that both KL and FGF23 signaling modulate TGF β-induced IL-8 secretion in CF bronchial epithelia. Thus, FGF23 and soluble KL levels were measured in plasma from 48 CF patients and in primary CF bronchial epithelial cells (CF-HBEC). CF patients showed increased FGF23 plasma levels, but KL levels were not different. In CF-HBEC, TGF-β increased KL secretion and upregulated FGF receptor (FGFR) 1. Despite increases in KL, TGF-β also increased IL-8 secretion via activation of FGFR1 and Smad 3 signaling. However, KL excess via overexpression or supplementation decreased IL-8 secretion by inhibiting Smad 3 phosphorylation. Here, we identify a novel signaling pathway contributing to IL-8 secretion in the CF bronchial epithelium with KL functioning as an endocrine and local anti-inflammatory mediator that antagonizes pro-inflammatory actions of FGF23 and TGF-β.

Original languageEnglish (US)
Article number14388
JournalScientific reports
Volume7
Issue number1
DOIs
StatePublished - Dec 1 2017

ASJC Scopus subject areas

  • General

Fingerprint Dive into the research topics of 'Klotho Inhibits Interleukin-8 Secretion from Cystic Fibrosis Airway Epithelia'. Together they form a unique fingerprint.

  • Cite this

    Krick, S., Baumlin, N., Aller, S. P., Aguiar, C., Grabner, A., Sailland, J., Mendes, E., Schmid, A., Qi, L., David, N. V., Geraghty, P., King, G., Birket, S. E., Rowe, S. M., Faul, C., & Salathe, M. (2017). Klotho Inhibits Interleukin-8 Secretion from Cystic Fibrosis Airway Epithelia. Scientific reports, 7(1), [14388]. https://doi.org/10.1038/s41598-017-14811-0