Thymic stromal lymphopoietin activity is increased in nasal polyps of patients with chronic rhinosinusitis - 02/09/13
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.
Le texte complet de cet article est disponible en PDF.Key words : Chronic rhinosinusitis, nasal polyps, thymic stromal lymphopoietin, epithelial cells, mast cells, TH2 cells, IL-5, proteases
Abbreviations used : CRS, CRSsNP, CRSwNP, DC, dsRNA, ILC2, IMDM, mDC, 2-ME, NHBE, NMFF, NP, PIC, PNEC, SCF, TLR, TSLP, TSLPR, UT
Plan
| Supported in part by National Institutes of Health grants R01 HL078860, R01 AI072570, and R37 HL068546 and by a grant from the Ernest S. Bazley Trust. |
|
| Disclosure of potential conflict of interest: J. A. Poposki and B. K. Tan have received research support from the National Institutes of Health (NIH). M. R. Comeau is employed by and has stock/stock options in Amgen and has patents related to TSLP. A. T. Peters has provided expert testimony on SJS/TEN and has received lecture fees from Baxter. L. C. Grammer has received research and travel support from the NIH; has received research support from the Food Allergy Network and S&C Electric and a Bazley Foundation grant; has received consultancy fees from Astellas Pharmaceuticals; is employed by Northwestern University and Northwestern Medical Faculty Foundation; has received lecture fees from the American Academy of Allergy, Asthma & Immunology; and receives royalties from Lippincott, UpToDate, BMU, and Elsevier. R. P. Schleimer has received research support from the NIH; has received consultancy fees from Intersect ENT, GlaxoSmithKline, Allakos, and Aurasense; and has stock/stock options in Allakos. A. Kato has received research support from the NIH. The rest of the authors declare that they have no relevant conflicts of interest. |
Vol 132 - N° 3
P. 593 - septembre 2013 Retour au numéro
Article précédent
- Increased expression of factor XIII-A in patients with chronic rhinosinusitis with nasal polyps
- Tetsuji Takabayashi, Atsushi Kato, Anju T. Peters, Kathryn E. Hulse, Lydia A. Suh, Roderick Carter, James Norton, Leslie C. Grammer, Bruce K. Tan, Rakesh K. Chandra, David B. Conley, Robert C. Kern, Shigeharu Fujieda, Robert P. Schleimer
- Establishment of the intestinal microbiota and its role for atopic dermatitis in early childhood
- John Penders, Kerstin Gerhold, Ellen E. Stobberingh, Carel Thijs, Kurt Zimmermann, Susanne Lau, Eckard Hamelmann
Bienvenue sur EM-consulte, la référence des professionnels de santé.
L’accès au texte intégral de cet article nécessite un abonnement.
Déjà abonné à cette revue ?