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

22 Citations (Scopus)

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

Fingerprint

Cytokine Receptor gp130
Interleukin-6
Association reactions
Interleukin-6 Receptors
Nasal Polyps
Tumor Necrosis Factor-alpha
Epithelial Cells
S100 Proteins
Asthma and Nasal Polyps
Nose
Restoration
Proteins
Enzyme-Linked Immunosorbent Assay
Air
Tissue
Liquids

Keywords

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

ASJC Scopus subject areas

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

Cite this

@article{944257dee5f241378d4f4b11dee4890a,
title = "Age-related increased prevalence of asthma and nasal polyps in chronic rhinosinusitis and its association with altered IL-6 trans-signaling",
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.",
keywords = "Aging, Chronic rhinosinusitis, Nasal polyps, S100A8/9, Soluble gp130",
author = "Cho, {Seong H.} and Kim, {Dae Woo} and Lee, {Sun H.} and Narasaiah Kolliputi and Hong, {Seung J.} and Lydia Suh and James Norton and Hulse, {Kathryn E.} and Sudarshan Seshadri and Conley, {David B.} and Kern, {Robert C.} and Tan, {Bruce K.} and Anju Peters and Grammer, {Leslie C.} and Schleimer, {Robert P.}",
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language = "English (US)",
volume = "53",
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}

Age-related increased prevalence of asthma and nasal polyps in chronic rhinosinusitis and its association with altered IL-6 trans-signaling. / Cho, Seong H.; Kim, Dae Woo; Lee, Sun H.; Kolliputi, Narasaiah; Hong, Seung J.; Suh, Lydia; Norton, James; Hulse, Kathryn E.; Seshadri, Sudarshan; Conley, David B.; Kern, Robert C.; Tan, Bruce K.; Peters, Anju; Grammer, Leslie C.; Schleimer, Robert P.

In: American journal of respiratory cell and molecular biology, Vol. 53, No. 5, 01.11.2015, p. 601-606.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Age-related increased prevalence of asthma and nasal polyps in chronic rhinosinusitis and its association with altered IL-6 trans-signaling

AU - Cho, Seong H.

AU - Kim, Dae Woo

AU - Lee, Sun H.

AU - Kolliputi, Narasaiah

AU - Hong, Seung J.

AU - Suh, Lydia

AU - Norton, James

AU - Hulse, Kathryn E.

AU - Seshadri, Sudarshan

AU - Conley, David B.

AU - Kern, Robert C.

AU - Tan, Bruce K.

AU - Peters, Anju

AU - Grammer, Leslie C.

AU - Schleimer, Robert P.

PY - 2015/11/1

Y1 - 2015/11/1

N2 - 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.

AB - 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.

KW - Aging

KW - Chronic rhinosinusitis

KW - Nasal polyps

KW - S100A8/9

KW - Soluble gp130

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