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

Publication ,  Journal Article
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 ...
Published in: Sci Rep
October 30, 2017

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.

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Published In

Sci Rep

DOI

EISSN

2045-2322

Publication Date

October 30, 2017

Volume

7

Issue

1

Start / End Page

14388

Location

England

Related Subject Headings

  • Transforming Growth Factor beta
  • Signal Transduction
  • Respiratory Mucosa
  • Rats
  • Mice
  • Male
  • Klotho Proteins
  • Interleukin-8
  • Inflammation
  • Humans
 

Citation

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Krick, S., Baumlin, N., Aller, S. P., Aguiar, C., Grabner, A., Sailland, J., … Salathe, M. (2017). Klotho Inhibits Interleukin-8 Secretion from Cystic Fibrosis Airway Epithelia. Sci Rep, 7(1), 14388. https://doi.org/10.1038/s41598-017-14811-0
Krick, Stefanie, Nathalie Baumlin, Sheyla Paredes Aller, Carolina Aguiar, Alexander Grabner, Juliette Sailland, Eliana Mendes, et al. “Klotho Inhibits Interleukin-8 Secretion from Cystic Fibrosis Airway Epithelia.Sci Rep 7, no. 1 (October 30, 2017): 14388. https://doi.org/10.1038/s41598-017-14811-0.
Krick S, Baumlin N, Aller SP, Aguiar C, Grabner A, Sailland J, et al. Klotho Inhibits Interleukin-8 Secretion from Cystic Fibrosis Airway Epithelia. Sci Rep. 2017 Oct 30;7(1):14388.
Krick, Stefanie, et al. “Klotho Inhibits Interleukin-8 Secretion from Cystic Fibrosis Airway Epithelia.Sci Rep, vol. 7, no. 1, Oct. 2017, p. 14388. Pubmed, doi:10.1038/s41598-017-14811-0.
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. Klotho Inhibits Interleukin-8 Secretion from Cystic Fibrosis Airway Epithelia. Sci Rep. 2017 Oct 30;7(1):14388.

Published In

Sci Rep

DOI

EISSN

2045-2322

Publication Date

October 30, 2017

Volume

7

Issue

1

Start / End Page

14388

Location

England

Related Subject Headings

  • Transforming Growth Factor beta
  • Signal Transduction
  • Respiratory Mucosa
  • Rats
  • Mice
  • Male
  • Klotho Proteins
  • Interleukin-8
  • Inflammation
  • Humans