Age-related increased prevalence of asthma and nasal polyps in chronic rhinosinusitis and its association with altered IL-6 trans-signaling

Seong H. Cho*, Dae Woo Kim, Sun H. Lee, Narasaiah Kolliputi, Seung J. Hong, Lydia Suh, James Norton, Kathryn E. Hulse, Sudarshan Seshadri, David B. Conley, Robert C. Kern, Bruce K. Tan, Anju Peters, Leslie C. Grammer, Robert P. Schleimer

*Corresponding author for this work

Research output: Contribution to journalArticle

27 Scopus citations

Abstract

We report that S100 proteins were reduced in patients with chronic rhinosinusitis (CRS). S100A8/9, which is important in epithelial barrier function, was particularly decreased in elderly patients with CRS. Epithelial expression of S100A8/9 is partly regulated by the IL-6 trans-signaling pathway. The goal of this study was to investigate whether or not age-related reduction of S100A8/9 in CRS is associated with blunting of IL-6 trans-signaling. The levels of IL-6, soluble IL-6 receptor (sIL-6R), soluble gp130 (sgp130), and S100A8/9 from control subjects (n = 10), and patients with CRS without nasal polyps (n = 13) and those with CRS with nasal polyps (CRSwNP) (n = 14), were measured by ELISA. Age-related differences in the level of each protein were investigated. Normal human bronchial epithelial cells were cultured in air-liquid interface and stimulated with IL-6/ sIL-6R and tumor necrosis factor (TNF)-a with or without the addition of sgp130, a natural inhibitor of IL-6 trans-signaling. There was a significant age-related decline in S100A8/9 and an increase in sgp130 in nasal tissue samples from patients with CRSwNP, although there was no age-related difference in IL-6/sIL-6R production. Additionally, expression of the S100A8/9 gene and protein was increased significantly by IL-6/sIL-6R plus TNF-α in normal human bronchial epithelial cells. This increase was blocked by sgp130. These results suggest that increased sgp130 in older patients may inhibit IL-6 trans-signaling, impair barrier function, and decrease S1008/9 production in elderly patients with CRSwNP. Restoration of barrier function by targeting sgp130 may be a novel treatment strategy.

Original languageEnglish (US)
Pages (from-to)601-606
Number of pages6
JournalAmerican journal of respiratory cell and molecular biology
Volume53
Issue number5
DOIs
StatePublished - Nov 1 2015

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Keywords

  • Aging
  • Chronic rhinosinusitis
  • Nasal polyps
  • S100A8/9
  • Soluble gp130

ASJC Scopus subject areas

  • Molecular Biology
  • Pulmonary and Respiratory Medicine
  • Clinical Biochemistry
  • Cell Biology

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