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Thymic stromal lymphopoietin activity is increased in nasal polyps of patients with chronic rhinosinusitis.
J Allergy Clin Immunol 2013; 132(3):593-600.e12JA

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.

Authors+Show Affiliations

Division of Allergy and Immunology, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, Ill.Division of Allergy and Immunology, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, Ill.Department of Otolaryngology-Head and Neck Surgery, Northwestern University Feinberg School of Medicine, Chicago, Ill.Department of Inflammation Research, Amgen, Seattle, Wash.Division of Allergy and Immunology, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, Ill.Division of Allergy and Immunology, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, Ill.Division of Allergy and Immunology, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, Ill.Division of Allergy and Immunology, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, Ill.Division of Allergy and Immunology, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, Ill.Division of Allergy and Immunology, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, Ill.Department of Otolaryngology-Head and Neck Surgery, Northwestern University Feinberg School of Medicine, Chicago, Ill.Department of Otolaryngology-Head and Neck Surgery, Northwestern University Feinberg School of Medicine, Chicago, Ill.Department of Otolaryngology-Head and Neck Surgery, Northwestern University Feinberg School of Medicine, Chicago, Ill.Division of Allergy and Immunology, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, Ill; Department of Otolaryngology-Head and Neck Surgery, Northwestern University Feinberg School of Medicine, Chicago, Ill.Division of Allergy and Immunology, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, Ill. Electronic address: a-kato@northwestern.edu.

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

23688414

Citation

Nagarkar, Deepti R., et al. "Thymic Stromal Lymphopoietin Activity Is Increased in Nasal Polyps of Patients With Chronic Rhinosinusitis." The Journal of Allergy and Clinical Immunology, vol. 132, no. 3, 2013, pp. 593-600.e12.
Nagarkar DR, Poposki JA, Tan BK, et al. Thymic stromal lymphopoietin activity is increased in nasal polyps of patients with chronic rhinosinusitis. J Allergy Clin Immunol. 2013;132(3):593-600.e12.
Nagarkar, D. R., Poposki, J. A., Tan, B. K., Comeau, M. R., Peters, A. T., Hulse, K. E., ... Kato, A. (2013). Thymic stromal lymphopoietin activity is increased in nasal polyps of patients with chronic rhinosinusitis. The Journal of Allergy and Clinical Immunology, 132(3), pp. 593-600.e12. doi:10.1016/j.jaci.2013.04.005.
Nagarkar DR, et al. Thymic Stromal Lymphopoietin Activity Is Increased in Nasal Polyps of Patients With Chronic Rhinosinusitis. J Allergy Clin Immunol. 2013;132(3):593-600.e12. PubMed PMID: 23688414.
* Article titles in AMA citation format should be in sentence-case
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, Y1 - 2013/05/17/ PY - 2012/08/31/received PY - 2013/04/03/revised PY - 2013/04/05/accepted PY - 2013/5/22/entrez PY - 2013/5/22/pubmed PY - 2013/11/13/medline KW - 2-ME KW - 2-Mercaptoethanol KW - CRS KW - CRSsNP KW - CRSwNP KW - Chronic rhinosinusitis KW - Chronic rhinosinusitis with nasal polyps KW - Chronic rhinosinusitis without nasal polyps KW - DC KW - Dendritic cell KW - Double-stranded RNA KW - IL-5 KW - ILC2 KW - IMDM KW - Iscove modified Dulbecco medium KW - Myeloid dendritic cell KW - NHBE KW - NMFF KW - NP KW - Nasal polyp KW - Normal human bronchial epithelial cell KW - Northwestern Medical Faculty Foundation KW - PIC KW - PNEC KW - Primary nasal epithelial cell KW - Protease inhibitor cocktail KW - SCF KW - Stem cell factor KW - T(H)2 cells KW - TLR KW - TSLP KW - TSLPR KW - Thymic stromal lymphopoietin KW - Thymic stromal lymphopoietin receptor KW - Toll-like receptor KW - Type 2 innate lymphoid cell KW - UT KW - Uncinate tissue KW - dsRNA KW - epithelial cells KW - mDC KW - mast cells KW - nasal polyps KW - proteases KW - thymic stromal lymphopoietin SP - 593 EP - 600.e12 JF - The Journal of allergy and clinical immunology JO - J. Allergy Clin. Immunol. VL - 132 IS - 3 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. SN - 1097-6825 UR - https://www.unboundmedicine.com/medline/citation/23688414/Thymic_stromal_lymphopoietin_activity_is_increased_in_nasal_polyps_of_patients_with_chronic_rhinosinusitis_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0091-6749(13)00593-9 DB - PRIME DP - Unbound Medicine ER -