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

JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY

卷:132

Article

Nagarkar, Deepti R.¹  Poposki, Julie A.¹  Tan, Bruce K.²  Comeau, Michael R.³  Peters, Anju T.¹  Hulse, Kathryn E.¹  Suh, Lydia A.¹  Norton, James¹  Harris, Kathleen E.¹  Grammer, Leslie C.¹  Chandra, Rakesh K.²  Conley, David B.²  Kern, Robert C.²  Schleimer, Robert P.^1,2  Kato, Atsushi¹ 

[1] Northwestern Univ, Feinberg Sch Med, Dept Med, Div Allergy & Immunol, Chicago, IL 60611 USA

[2] Northwestern Univ, Feinberg Sch Med, Dept Otolaryngol Head & Neck Surg, Chicago, IL 60611 USA

[3] Dept Inflammat Res, Seattle, WA USA

关键词: Chronic rhinosinusitis;    nasal polyps;    thymic stromal lymphopoietin;    epithelial cells;    mast cells;    T(H)2 cells;    IL-5;    proteases;   

DOI  :  10.1016/j.jaci.2013.04.005

来源: Elsevier

【 摘 要 】

Background: Chronic rhinosinusitis with nasal polyps (CRSwNP) is associated with T(H)2-dominant inflammation. Thymic stromal lymphopoietin (TSLP) is a cytokine that triggers dendritic cell-mediated T(H)2 inflammatory responses and that enhances IL-1-dependent T(H)2 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-1 beta-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.

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