Decreased expression of type I (IFN-β) and type III (IFN-λ) interferons and interferon-stimulated genes in patients with chronic rhinosinusitis with and without nasal polyps

Jae Woong Hwang, Ki Jeong Lee, In Hak Choi, Hye Min Han, Tae Hoon Kim, Sang Hag Lee

Research output: Contribution to journalArticle

Abstract

Background: Little is known about antiviral responses in the sinonasal mucosal tissue of patients with chronic rhinosinusitis (CRS). Objective: we investigated the presence of virus and the expression of Toll-like receptor (TLR) 3, TLR7, and interferon and interferon-stimulated genes (ISGs) in healthy mucosal tissue of control subjects and the inflammatory sinus mucosal tissue of CRS patients, and evaluated whether levels of interferons and ISGs might be affected by CRS-related cytokines and by treatment with macrolides, dexamethasone, or TLR3 and TLR7 agonists. Methods: The presence of virus in the sinonasal mucosa was evaluated with real-time PCR. The expression of interferons and ISGs in the sinonasal mucosa and in cultured epithelial cells treated with TH1 and TH2 cytokines, macrolides, dexamethasone, or TLR3 and TLR7 agonists were evaluated with real-time PCR and Western blotting. The expression of TLR3 and TLR7 in the sinonasal mucosa were evaluated with immunohistochemistry. Results: Respiratory viruses were detected in 15% of samples. Interferons and ISGs are expressed in normal mucosa, but their levels were decreased in patients with CRS. Interferon and ISG levels were upregulated in cells treated with macrolides, dexamethasone, or TLR3 agonist, but some were decreased in cytokine-treated cells. TLR3 and TLR7 levels showed no significant difference between normal and inflammatory sinus mucosal tissue. Conclusion: These results suggest that decreased levels of interferons and ISGs in patients with CRS might contribute to impairment of the antiviral innate response in inflammatory sinonasal epithelial cells. Macrolides and glucocorticoids might provide positive effects on the treatment of CRS by upregulating interferon and ISG expression.

Original languageEnglish
JournalJournal of Allergy and Clinical Immunology
DOIs
Publication statusAccepted/In press - 2019 Jan 1

Fingerprint

Nasal Polyps
Interferons
Mucous Membrane
Genes
Macrolides
Dexamethasone
Cytokines
Viruses
Antiviral Agents
Real-Time Polymerase Chain Reaction
Epithelial Cells
Toll-Like Receptor 3
Glucocorticoids

Keywords

  • chronic rhinosinusitis with nasal polyps
  • chronic rhinosinusitis without nasal polyps
  • interferon-stimulated gene
  • myxovirus resistance 1
  • oligoadenylate synthetase
  • Type I interferon
  • type III interferon
  • viperin

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

@article{13e7429dee7b4e0e93dbafe210e60d19,
title = "Decreased expression of type I (IFN-β) and type III (IFN-λ) interferons and interferon-stimulated genes in patients with chronic rhinosinusitis with and without nasal polyps",
abstract = "Background: Little is known about antiviral responses in the sinonasal mucosal tissue of patients with chronic rhinosinusitis (CRS). Objective: we investigated the presence of virus and the expression of Toll-like receptor (TLR) 3, TLR7, and interferon and interferon-stimulated genes (ISGs) in healthy mucosal tissue of control subjects and the inflammatory sinus mucosal tissue of CRS patients, and evaluated whether levels of interferons and ISGs might be affected by CRS-related cytokines and by treatment with macrolides, dexamethasone, or TLR3 and TLR7 agonists. Methods: The presence of virus in the sinonasal mucosa was evaluated with real-time PCR. The expression of interferons and ISGs in the sinonasal mucosa and in cultured epithelial cells treated with TH1 and TH2 cytokines, macrolides, dexamethasone, or TLR3 and TLR7 agonists were evaluated with real-time PCR and Western blotting. The expression of TLR3 and TLR7 in the sinonasal mucosa were evaluated with immunohistochemistry. Results: Respiratory viruses were detected in 15{\%} of samples. Interferons and ISGs are expressed in normal mucosa, but their levels were decreased in patients with CRS. Interferon and ISG levels were upregulated in cells treated with macrolides, dexamethasone, or TLR3 agonist, but some were decreased in cytokine-treated cells. TLR3 and TLR7 levels showed no significant difference between normal and inflammatory sinus mucosal tissue. Conclusion: These results suggest that decreased levels of interferons and ISGs in patients with CRS might contribute to impairment of the antiviral innate response in inflammatory sinonasal epithelial cells. Macrolides and glucocorticoids might provide positive effects on the treatment of CRS by upregulating interferon and ISG expression.",
keywords = "chronic rhinosinusitis with nasal polyps, chronic rhinosinusitis without nasal polyps, interferon-stimulated gene, myxovirus resistance 1, oligoadenylate synthetase, Type I interferon, type III interferon, viperin",
author = "Hwang, {Jae Woong} and Lee, {Ki Jeong} and Choi, {In Hak} and Han, {Hye Min} and Kim, {Tae Hoon} and Lee, {Sang Hag}",
year = "2019",
month = "1",
day = "1",
doi = "10.1016/j.jaci.2019.08.010",
language = "English",
journal = "Journal of Allergy and Clinical Immunology",
issn = "0091-6749",
publisher = "Mosby Inc.",

}

TY - JOUR

T1 - Decreased expression of type I (IFN-β) and type III (IFN-λ) interferons and interferon-stimulated genes in patients with chronic rhinosinusitis with and without nasal polyps

AU - Hwang, Jae Woong

AU - Lee, Ki Jeong

AU - Choi, In Hak

AU - Han, Hye Min

AU - Kim, Tae Hoon

AU - Lee, Sang Hag

PY - 2019/1/1

Y1 - 2019/1/1

N2 - Background: Little is known about antiviral responses in the sinonasal mucosal tissue of patients with chronic rhinosinusitis (CRS). Objective: we investigated the presence of virus and the expression of Toll-like receptor (TLR) 3, TLR7, and interferon and interferon-stimulated genes (ISGs) in healthy mucosal tissue of control subjects and the inflammatory sinus mucosal tissue of CRS patients, and evaluated whether levels of interferons and ISGs might be affected by CRS-related cytokines and by treatment with macrolides, dexamethasone, or TLR3 and TLR7 agonists. Methods: The presence of virus in the sinonasal mucosa was evaluated with real-time PCR. The expression of interferons and ISGs in the sinonasal mucosa and in cultured epithelial cells treated with TH1 and TH2 cytokines, macrolides, dexamethasone, or TLR3 and TLR7 agonists were evaluated with real-time PCR and Western blotting. The expression of TLR3 and TLR7 in the sinonasal mucosa were evaluated with immunohistochemistry. Results: Respiratory viruses were detected in 15% of samples. Interferons and ISGs are expressed in normal mucosa, but their levels were decreased in patients with CRS. Interferon and ISG levels were upregulated in cells treated with macrolides, dexamethasone, or TLR3 agonist, but some were decreased in cytokine-treated cells. TLR3 and TLR7 levels showed no significant difference between normal and inflammatory sinus mucosal tissue. Conclusion: These results suggest that decreased levels of interferons and ISGs in patients with CRS might contribute to impairment of the antiviral innate response in inflammatory sinonasal epithelial cells. Macrolides and glucocorticoids might provide positive effects on the treatment of CRS by upregulating interferon and ISG expression.

AB - Background: Little is known about antiviral responses in the sinonasal mucosal tissue of patients with chronic rhinosinusitis (CRS). Objective: we investigated the presence of virus and the expression of Toll-like receptor (TLR) 3, TLR7, and interferon and interferon-stimulated genes (ISGs) in healthy mucosal tissue of control subjects and the inflammatory sinus mucosal tissue of CRS patients, and evaluated whether levels of interferons and ISGs might be affected by CRS-related cytokines and by treatment with macrolides, dexamethasone, or TLR3 and TLR7 agonists. Methods: The presence of virus in the sinonasal mucosa was evaluated with real-time PCR. The expression of interferons and ISGs in the sinonasal mucosa and in cultured epithelial cells treated with TH1 and TH2 cytokines, macrolides, dexamethasone, or TLR3 and TLR7 agonists were evaluated with real-time PCR and Western blotting. The expression of TLR3 and TLR7 in the sinonasal mucosa were evaluated with immunohistochemistry. Results: Respiratory viruses were detected in 15% of samples. Interferons and ISGs are expressed in normal mucosa, but their levels were decreased in patients with CRS. Interferon and ISG levels were upregulated in cells treated with macrolides, dexamethasone, or TLR3 agonist, but some were decreased in cytokine-treated cells. TLR3 and TLR7 levels showed no significant difference between normal and inflammatory sinus mucosal tissue. Conclusion: These results suggest that decreased levels of interferons and ISGs in patients with CRS might contribute to impairment of the antiviral innate response in inflammatory sinonasal epithelial cells. Macrolides and glucocorticoids might provide positive effects on the treatment of CRS by upregulating interferon and ISG expression.

KW - chronic rhinosinusitis with nasal polyps

KW - chronic rhinosinusitis without nasal polyps

KW - interferon-stimulated gene

KW - myxovirus resistance 1

KW - oligoadenylate synthetase

KW - Type I interferon

KW - type III interferon

KW - viperin

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U2 - 10.1016/j.jaci.2019.08.010

DO - 10.1016/j.jaci.2019.08.010

M3 - Article

C2 - 31449915

AN - SCOPUS:85072536626

JO - Journal of Allergy and Clinical Immunology

JF - Journal of Allergy and Clinical Immunology

SN - 0091-6749

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