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 language | English (US) |
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Pages (from-to) | 601-606 |
Number of pages | 6 |
Journal | American journal of respiratory cell and molecular biology |
Volume | 53 |
Issue number | 5 |
DOIs | |
State | Published - Nov 2015 |
Funding
This work was supported by the National Institutes of Health (NIH) 1K23AI110731, the American Heart Association (11SDG7590063), and The Ernest Bazley Foundation (S.H.C.); R37HL068546, R01HL078860, P01AI106683, and The Ernest Bazley Foundation (R.P.S.); and NIH R01HL105932 (N.K.).
Keywords
- Aging
- Chronic rhinosinusitis
- Nasal polyps
- S100A8/9
- Soluble gp130
ASJC Scopus subject areas
- Molecular Biology
- Pulmonary and Respiratory Medicine
- Clinical Biochemistry
- Cell Biology