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

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

31 Scopus citations


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
Issue number1
StatePublished - Dec 1 2017

ASJC Scopus subject areas

  • General


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