Prolonged allergen exposure is associated with increased thymic stromal lymphopoietin expression and Th2-skewing in mouse models of chronic rhinosinusitis.
Chronic rhinosinusitis (CRS) is characterized by a dysfunctional host-environment interaction at the nasal mucosa. Contributions of host susceptibility factors such as atopy and aspirin sensitivity to CRS pathophysiology are well established. However, clinical studies on the effects of environmental factors are limited. This study investigates the histological and immunological effects of allergen exposure duration in animal models.



Animal study.



A murine model for CRS with nasal polypoid lesions was induced by instilling ovalbumin/staphylococcal enterotoxin B (SEB) into murine nasal cavities for 12 (short term) or 24 weeks (long term). Histopathological changes were observed. Interleukin (IL)-4, IL-17A, IL-10, and interferon (INF)-γ levels from nasal lavage fluid were measured using enzyme-linked immunosorbent assay. Gene expressions of IL-25, thymic stromal lymphopoietin (TSLP), IL-4, IL-5, INF-γ, C-C motif chemokine ligand (CCL)-11, CCL-24, C-X-C motif chemokine ligand (CXCL)-1, CXCL-2, intercellular adhesion molecule 1, vascular cell adhesion molecule 1, matrix metallopeptidase (MMP)-7, and tissue inhibitor of metalloproteinase (TIMP)-3 were analyzed from the nasal mucosa.



Long-term CRS models exhibited increased polypoid lesions, edematous mucosal thickness, and eosinophil infiltration compared with short-term models and showed a higher IL-10 level but lower IFN-γ and IL-17A protein levels. Moreover, CCL-24 and MMP-7 gene expressions increased whereas TIMP-3 expression decreased in long-term models compared to controls and short-term models. IL-25 and TSLP expressions were upregulated at mRNA and protein levels in short-term and long-term CRS models, respectively. Furthermore, TSLP mRNA expression was positively associated with IL-5 (r = 0.8754) and inversely correlated to IFN-γ (r = -0.7212) in CRS models.



Prolonged allergen exposure in ovalbumin/SEB-induced CRS models maintains Th2 inflammation and reduces Th1 inflammation, which was associated with upregulation of TSLP.



NA Laryngoscope, 126:E265-E272, 2016.
Department of Otorhinolaryngology-Head and Neck Surgery, Boramae Medical Center, Seoul National University College of Medicine, Seoul, Korea.
Dae Woo
DW
Kim
Department of Otorhinolaryngology-Head and Neck Surgery, Boramae Medical Center, Seoul National University College of Medicine, Seoul, Korea.
Kyoung Mi
KM
Eun
Department of Otorhinolaryngology-Head and Neck Surgery, Boramae Medical Center, Seoul National University College of Medicine, Seoul, Korea.
Hong Ryul
HR
Jin
Division of Allergy-Immunology, Department of Internal Medicine, University of South Florida Morsani College of Medicine, Tampa, Florida, U.S.A.
Seong H
SH
Cho
Department of Otorhinolaryngology-Head and Neck Surgery, Chuncheon Sacred Heart Hospital and Nano-Bio Regenerative Medical Institute, Hallym University College of Medicine, Chuncheon, Korea.
Dong-Kyu
DK
Kim
D000485:Allergens / Q000008:administration & dosage / Q000276:immunology*; D000818:Animals; D002908:Chronic Disease; D016207:Cytokines / Q000096:biosynthesis*; D004195:Disease Models, Animal; D005260:Female; D051379:Mice; D008807:Mice, Inbred BALB C; D012220:Rhinitis / Q000276:immunology* / Q000378:metabolism*; D012852:Sinusitis / Q000276:immunology* / Q000378:metabolism*; D018418:Th2 Cells / Q000276:immunology*; D013997:Time Factors; D000094632:Thymic Stromal Lymphopoietin
D000485:Allergens; D016207:Cytokines; D000094632:Thymic Stromal Lymphopoietin; C000721967:TSLP protein, mouse
Animal model; eosinophil; nasal polyps; rhinosinusitis; thymic stromal lymphopoietin