Age-related increased prevalence of asthma and nasal polyps in chronic rhinosinusitis and its association with altered IL-6 trans-signaling.
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)-α 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.
1 Division of Allergy-Immunology, Department of Medicine, and.|2 Division of Allergy-Immunology, Department of Internal Medicine, University of South Florida College of Medicine, Tampa, Florida.|3 Division of Rheumatology, Department of Medicine, Kyung Hee University School of Medicine, Seoul, Korea; and.
Seong H
SH
Cho
2 Division of Allergy-Immunology, Department of Internal Medicine, University of South Florida College of Medicine, Tampa, Florida.|4 Department of Otorhinolaryngology-Head and Neck Surgery, Boramae Medical Center, Seoul National University College of Medicine, Seoul, Korea.
Dae Woo
DW
Kim
1 Division of Allergy-Immunology, Department of Medicine, and.
Sun H
SH
Lee
2 Division of Allergy-Immunology, Department of Internal Medicine, University of South Florida College of Medicine, Tampa, Florida.
Narasaiah
N
Kolliputi
3 Division of Rheumatology, Department of Medicine, Kyung Hee University School of Medicine, Seoul, Korea; and.
Seung J
SJ
Hong
1 Division of Allergy-Immunology, Department of Medicine, and.
Lydia
L
Suh
1 Division of Allergy-Immunology, Department of Medicine, and.
James
J
Norton
1 Division of Allergy-Immunology, Department of Medicine, and.
Kathryn E
KE
Hulse
1 Division of Allergy-Immunology, Department of Medicine, and.
Sudarshan
S
Seshadri
5 Department of Otolaryngology, Northwestern Feinberg School of Medicine, Chicago, Illinois.
David B
DB
Conley
5 Department of Otolaryngology, Northwestern Feinberg School of Medicine, Chicago, Illinois.
Robert C
RC
Kern
5 Department of Otolaryngology, Northwestern Feinberg School of Medicine, Chicago, Illinois.
Bruce K
BK
Tan
1 Division of Allergy-Immunology, Department of Medicine, and.
Anju
A
Peters
1 Division of Allergy-Immunology, Department of Medicine, and.
Leslie C
LC
Grammer
1 Division of Allergy-Immunology, Department of Medicine, and.|5 Department of Otolaryngology, Northwestern Feinberg School of Medicine, Chicago, Illinois.
Robert P
RP
Schleimer
D000328:Adult; D000367:Age Factors; D000368:Aged; D001249:Asthma / Q000150:complications / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D001980:Bronchi / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D040501:Calgranulin A / Q000819:agonists / Q000235:genetics / Q000276:immunology; D040502:Calgranulin B / Q000235:genetics / Q000276:immunology; D016022:Case-Control Studies; D002478:Cells, Cultured; D002908:Chronic Disease; D050822:Cytokine Receptor gp130 / Q000235:genetics / Q000276:immunology* / Q000494:pharmacology; D004847:Epithelial Cells / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D015850:Interleukin-6 / Q000235:genetics / Q000276:immunology* / Q000494:pharmacology; D008297:Male; D008875:Middle Aged; D009298:Nasal Polyps / Q000150:complications / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D019947:Receptors, Interleukin-6 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000276:immunology; D012220:Rhinitis / Q000150:complications / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D015398:Signal Transduction; D012852:Sinusitis / Q000150:complications / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000276:immunology / Q000494:pharmacology; D000093242:Interleukin-6 Inhibitors
D040501:Calgranulin A; D040502:Calgranulin B; D050822:Cytokine Receptor gp130; D015850:Interleukin-6; D019947:Receptors, Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D000093242:Interleukin-6 Inhibitors; C508600:IL6 protein, human
S100A8/9; aging; chronic rhinosinusitis; nasal polyps; soluble gp130