Klotho Inhibits Interleukin-8 Secretion from Cystic Fibrosis Airway Epithelia.

Published online

Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • Krick, S; Baumlin, N; Aller, SP; Aguiar, C; Grabner, A; Sailland, J; Mendes, E; Schmid, A; Qi, L; David, NV; Geraghty, P; King, G; Birket, SE; Rowe, SM; Faul, C; Salathe, M

Published Date

  • October 30, 2017

Published In

Volume / Issue

  • 7 / 1

Start / End Page

  • 14388 -

PubMed ID

  • 29085059

Pubmed Central ID

  • 29085059

Electronic International Standard Serial Number (EISSN)

  • 2045-2322

Digital Object Identifier (DOI)

  • 10.1038/s41598-017-14811-0

Language

  • eng

Conference Location

  • England