Thymic stromal lymphopoietin activity is increased in nasal polyps of patients with chronic rhinosinusitis

Deepti R. Nagarkar, Julie A. Poposki, Bruce K. Tan, Michael R. Comeau, Anju T. Peters, Kathryn E. Hulse, Lydia A. Suh, James Norton, Kathleen E. Harris, Leslie C. Grammer, Rakesh K. Chandra, David B. Conley, Robert C. Kern, Robert P. Schleimer, Atsushi Kato*

*Corresponding author for this work

Research output: Contribution to journalArticle

111 Citations (Scopus)

Abstract

Background: Chronic rhinosinusitis with nasal polyps (CRSwNP) is associated with TH2-dominant inflammation. Thymic stromal lymphopoietin (TSLP) is a cytokine that triggers dendritic cell-mediated TH2 inflammatory responses and that enhances IL-1-dependent TH2 cytokine production in mast cells. Although increased TSLP mRNA levels have been found in nasal polyps (NPs), expression of TSLP protein and its function in patients with chronic rhinosinusitis (CRS) have not been fully explored. Objectives: The objective of this study was to investigate the role of TSLP in patients with CRS. Methods: We investigated the presence and stability of TSLP protein in NPs using ELISA and Western blotting and investigated the function of TSLP in nasal tissue extracts with a bioassay based on activation of human mast cells. Results: Although TSLP mRNA levels were significantly increased in NP tissue from patients with CRSwNP compared with uncinate tissue from patients with CRS or control subjects, TSLP protein was significantly decreased in NP tissue, as detected by using the commercial ELISA kit. We found that recombinant TSLP was time-dependently degraded by NP extracts, and this degradation was completely inhibited by a protease inhibitor cocktail, suggesting that TSLP is sensitive to tissue proteases. Interestingly, NP extract-treated TSLP had higher activity in mast cells, although the amount of full-length TSLP was reduced up to 85%. NP extracts significantly enhanced IL-1β-dependent IL-5 production in mast cells compared with uncinate tissue homogenates, and responses were significantly inhibited by anti-TSLP, suggesting that NPs contain biologically relevant levels of TSLP activity. Conclusion: TSLP and its metabolic products might play an important role in the inflammation seen in patients with CRSwNP.

Original languageEnglish (US)
JournalJournal of Allergy and Clinical Immunology
Volume132
Issue number3
DOIs
StatePublished - Jan 1 2013

Fingerprint

Nasal Polyps
Mast Cells
thymic stromal lymphopoietin
Interleukin-1
Enzyme-Linked Immunosorbent Assay
Cytokines
Inflammation
Messenger RNA
Proteins
Tissue Extracts
Interleukin-5
Protease Inhibitors
Nose

Keywords

  • Chronic rhinosinusitis
  • IL-5
  • epithelial cells
  • mast cells
  • nasal polyps
  • proteases
  • thymic stromal lymphopoietin

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

@article{94de8ebe471241ae98b4f4ecab772928,
title = "Thymic stromal lymphopoietin activity is increased in nasal polyps of patients with chronic rhinosinusitis",
abstract = "Background: Chronic rhinosinusitis with nasal polyps (CRSwNP) is associated with TH2-dominant inflammation. Thymic stromal lymphopoietin (TSLP) is a cytokine that triggers dendritic cell-mediated TH2 inflammatory responses and that enhances IL-1-dependent TH2 cytokine production in mast cells. Although increased TSLP mRNA levels have been found in nasal polyps (NPs), expression of TSLP protein and its function in patients with chronic rhinosinusitis (CRS) have not been fully explored. Objectives: The objective of this study was to investigate the role of TSLP in patients with CRS. Methods: We investigated the presence and stability of TSLP protein in NPs using ELISA and Western blotting and investigated the function of TSLP in nasal tissue extracts with a bioassay based on activation of human mast cells. Results: Although TSLP mRNA levels were significantly increased in NP tissue from patients with CRSwNP compared with uncinate tissue from patients with CRS or control subjects, TSLP protein was significantly decreased in NP tissue, as detected by using the commercial ELISA kit. We found that recombinant TSLP was time-dependently degraded by NP extracts, and this degradation was completely inhibited by a protease inhibitor cocktail, suggesting that TSLP is sensitive to tissue proteases. Interestingly, NP extract-treated TSLP had higher activity in mast cells, although the amount of full-length TSLP was reduced up to 85{\%}. NP extracts significantly enhanced IL-1β-dependent IL-5 production in mast cells compared with uncinate tissue homogenates, and responses were significantly inhibited by anti-TSLP, suggesting that NPs contain biologically relevant levels of TSLP activity. Conclusion: TSLP and its metabolic products might play an important role in the inflammation seen in patients with CRSwNP.",
keywords = "Chronic rhinosinusitis, IL-5, epithelial cells, mast cells, nasal polyps, proteases, thymic stromal lymphopoietin",
author = "Nagarkar, {Deepti R.} and Poposki, {Julie A.} and Tan, {Bruce K.} and Comeau, {Michael R.} and Peters, {Anju T.} and Hulse, {Kathryn E.} and Suh, {Lydia A.} and James Norton and Harris, {Kathleen E.} and Grammer, {Leslie C.} and Chandra, {Rakesh K.} and Conley, {David B.} and Kern, {Robert C.} and Schleimer, {Robert P.} and Atsushi Kato",
year = "2013",
month = "1",
day = "1",
doi = "10.1016/j.jaci.2013.04.005",
language = "English (US)",
volume = "132",
journal = "Journal of Allergy and Clinical Immunology",
issn = "0091-6749",
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Thymic stromal lymphopoietin activity is increased in nasal polyps of patients with chronic rhinosinusitis. / Nagarkar, Deepti R.; Poposki, Julie A.; Tan, Bruce K.; Comeau, Michael R.; Peters, Anju T.; Hulse, Kathryn E.; Suh, Lydia A.; Norton, James; Harris, Kathleen E.; Grammer, Leslie C.; Chandra, Rakesh K.; Conley, David B.; Kern, Robert C.; Schleimer, Robert P.; Kato, Atsushi.

In: Journal of Allergy and Clinical Immunology, Vol. 132, No. 3, 01.01.2013.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Thymic stromal lymphopoietin activity is increased in nasal polyps of patients with chronic rhinosinusitis

AU - Nagarkar, Deepti R.

AU - Poposki, Julie A.

AU - Tan, Bruce K.

AU - Comeau, Michael R.

AU - Peters, Anju T.

AU - Hulse, Kathryn E.

AU - Suh, Lydia A.

AU - Norton, James

AU - Harris, Kathleen E.

AU - Grammer, Leslie C.

AU - Chandra, Rakesh K.

AU - Conley, David B.

AU - Kern, Robert C.

AU - Schleimer, Robert P.

AU - Kato, Atsushi

PY - 2013/1/1

Y1 - 2013/1/1

N2 - Background: Chronic rhinosinusitis with nasal polyps (CRSwNP) is associated with TH2-dominant inflammation. Thymic stromal lymphopoietin (TSLP) is a cytokine that triggers dendritic cell-mediated TH2 inflammatory responses and that enhances IL-1-dependent TH2 cytokine production in mast cells. Although increased TSLP mRNA levels have been found in nasal polyps (NPs), expression of TSLP protein and its function in patients with chronic rhinosinusitis (CRS) have not been fully explored. Objectives: The objective of this study was to investigate the role of TSLP in patients with CRS. Methods: We investigated the presence and stability of TSLP protein in NPs using ELISA and Western blotting and investigated the function of TSLP in nasal tissue extracts with a bioassay based on activation of human mast cells. Results: Although TSLP mRNA levels were significantly increased in NP tissue from patients with CRSwNP compared with uncinate tissue from patients with CRS or control subjects, TSLP protein was significantly decreased in NP tissue, as detected by using the commercial ELISA kit. We found that recombinant TSLP was time-dependently degraded by NP extracts, and this degradation was completely inhibited by a protease inhibitor cocktail, suggesting that TSLP is sensitive to tissue proteases. Interestingly, NP extract-treated TSLP had higher activity in mast cells, although the amount of full-length TSLP was reduced up to 85%. NP extracts significantly enhanced IL-1β-dependent IL-5 production in mast cells compared with uncinate tissue homogenates, and responses were significantly inhibited by anti-TSLP, suggesting that NPs contain biologically relevant levels of TSLP activity. Conclusion: TSLP and its metabolic products might play an important role in the inflammation seen in patients with CRSwNP.

AB - Background: Chronic rhinosinusitis with nasal polyps (CRSwNP) is associated with TH2-dominant inflammation. Thymic stromal lymphopoietin (TSLP) is a cytokine that triggers dendritic cell-mediated TH2 inflammatory responses and that enhances IL-1-dependent TH2 cytokine production in mast cells. Although increased TSLP mRNA levels have been found in nasal polyps (NPs), expression of TSLP protein and its function in patients with chronic rhinosinusitis (CRS) have not been fully explored. Objectives: The objective of this study was to investigate the role of TSLP in patients with CRS. Methods: We investigated the presence and stability of TSLP protein in NPs using ELISA and Western blotting and investigated the function of TSLP in nasal tissue extracts with a bioassay based on activation of human mast cells. Results: Although TSLP mRNA levels were significantly increased in NP tissue from patients with CRSwNP compared with uncinate tissue from patients with CRS or control subjects, TSLP protein was significantly decreased in NP tissue, as detected by using the commercial ELISA kit. We found that recombinant TSLP was time-dependently degraded by NP extracts, and this degradation was completely inhibited by a protease inhibitor cocktail, suggesting that TSLP is sensitive to tissue proteases. Interestingly, NP extract-treated TSLP had higher activity in mast cells, although the amount of full-length TSLP was reduced up to 85%. NP extracts significantly enhanced IL-1β-dependent IL-5 production in mast cells compared with uncinate tissue homogenates, and responses were significantly inhibited by anti-TSLP, suggesting that NPs contain biologically relevant levels of TSLP activity. Conclusion: TSLP and its metabolic products might play an important role in the inflammation seen in patients with CRSwNP.

KW - Chronic rhinosinusitis

KW - IL-5

KW - epithelial cells

KW - mast cells

KW - nasal polyps

KW - proteases

KW - thymic stromal lymphopoietin

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U2 - 10.1016/j.jaci.2013.04.005

DO - 10.1016/j.jaci.2013.04.005

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VL - 132

JO - Journal of Allergy and Clinical Immunology

JF - Journal of Allergy and Clinical Immunology

SN - 0091-6749

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