Molecular and Cellular Biochemistry

, Volume 373, Issue 1–2, pp 241–246 | Cite as

Ubiquitin E3 ligase TNFIAP3 mediates endosome/lysosome fusion in nasal epithelial cells

  • Xingqiang Gao


The nasal epithelial barrier dysfunction is associated with the pathogenesis of nasal allergy; the causative factors are to be further elucidated. Ubiquitin E3 ligase TNFIAP3 (TNFIAP3, in short) plays a role in the maintenance of the homeostasis in the body. This study aims to elucidate the role of TNFIAP3 in the degradation of endocytic substances in nasal epithelial cells. The nasal epithelial cell line, RPMI 2650 cells (RPC), was cultured into monolayers in transwells. The endocytosis of staphylococcal enterotoxin B (SEB) by RPC monolayers was assessed by enzyme-linked immunoassay. The endocytosis of SEB-triggered endosome/lysosome fusion was observed by immunocytochemistry. The results showed that RPC monolayers expressed TNFIAP3 upon the endocytosis of SEB. Deficiency of TNFIAP3 resulted in abundant SEBs being transported to the basal chambers of transwells via the intracellular pathway. In the TNFIAP3-sufficient RPC, SEB-carrying endosomes fused with lysosomes were observed. The TNFIAP3-deficient RPC showed few SEB-carrying endosomes fused with lysosomes. In summary, TNFIAP3 plays an important role in tethering endosomes to lysosomes in RPC.


Nose Epithelium Barrier function Endosome Lysosome 


  1. 1.
    Flöistrup H, Swartz J, Bergström A, Alm JS, Scheynius A, van Hage M, Waser M, Braun-Fahrländer C, Schram-Bijkerk D, Huber M, Zutavern A, von Mutius E, Ublagger E, Riedler J, Michaels KB, Pershagen G, Parsifal Study Group (2006) Allergic disease and sensitization in Steiner school children. J Allergy Clin Immunol 117:59–66PubMedCrossRefGoogle Scholar
  2. 2.
    Kjaer HF, Eller E, Høst A, Andersen KE, Bindslev-Jensen C (2008) The prevalence of allergic diseases in an unselected group of 6-year-old children. The DARC birth cohort study. Pediatr Allergy Immunol 19:737–745PubMedCrossRefGoogle Scholar
  3. 3.
    Mir E, Panjabi C, Shah A (2012) Impact of allergic rhinitis in school going children. Asia Pac Allergy 2:93–100PubMedCrossRefGoogle Scholar
  4. 4.
    Wise SK, Ahn CN, Schlosser RJ (2009) Localized immunoglobulin E expression in allergic rhinitis and nasal polyposis. Curr Opin Otolaryngol Head Neck Surg 17:216–222PubMedCrossRefGoogle Scholar
  5. 5.
    Zhang N, Holtappels G, Gevaert P, Patou J, Dhaliwal B, Gould H, Bachert C (2011) Mucosal tissue polyclonal IgE is functional in response to allergen and SEB. Allergy 66:141–148PubMedCrossRefGoogle Scholar
  6. 6.
    Tang X, Sun R, Hong S, Hu G, Yang Y (2011) Repeated intranasal instillation with staphylococcal enterotoxin B induces nasal allergic inflammation in guinea pigs. Am J Rhinol Allergy 25:176–181PubMedCrossRefGoogle Scholar
  7. 7.
    Nurtanio N, Yang PC (2011) Role of TIM-4 in innate or adaptive immune response. N Am J Med Sci 3:217–221PubMedCrossRefGoogle Scholar
  8. 8.
    Feng BS, Chen X, He SH, Zheng PY, Foster J, Xing Z, Bienenstock J, Yang PC (2008) Disruption of T-cell immunoglobulin and mucin domain molecule (TIM)-1/TIM4 interaction as a therapeutic strategy in a dendritic cellΓÇôinduced peanut allergy model. J Allergy Clin Immunol 122:55–61PubMedCrossRefGoogle Scholar
  9. 9.
    Kou K, Aihara M, Matsunaga T, Chen H, Taguri M, Morita S, Fujita H, Yamaguchi Y, Kambara T, Ikezawa Z (2012) Association of serum interleukin-18 and other biomarkers with disease severity in adults with atopic dermatitis. Arch Dermatol Res 304:305–312PubMedCrossRefGoogle Scholar
  10. 10.
    Zhang N, Holtappels G, Gevaert P, Patou J, Dhaliwal B, Gould H, Bachert C (2011) Mucosal tissue polyclonal IgE is functional in response to allergen and SEB. Allergy 66:141–148PubMedCrossRefGoogle Scholar
  11. 11.
    Hammer GE, Turer EE, Taylor KE, Fang CJ, Advincula R, Oshima S, Barrera J, Huang EJ, Hou B, Malynn BA, Reizis B, DeFranco A, Criswell LA, Nakamura MC, Ma A (2011) Expression of TNFIAP3 by dendritic cells preserves immune homeostasis and prevents colitis and spondyloarthritis. Nat Immunol 12:1184–1193PubMedCrossRefGoogle Scholar
  12. 12.
    Vereecke L, Sze M, McGuire C, Rogiers B, Chu Y, Schmidt-Supprian M, Pasparakis M, Beyaert R, van Loo G (2010) Enterocyte-specific TNFIAP3 deficiency sensitizes to tumor necrosis factor-induced toxicity and experimental colitis. J Exp Med 207:1513–1523PubMedCrossRefGoogle Scholar
  13. 13.
    Li L, Soetandyo N, Wang Q, Ye Y (2009) The zinc finger protein TNFIAP3 targets TRAF2 to the lysosomes for degradation. Biochim Biophys Acta 1793:346–353PubMedCrossRefGoogle Scholar
  14. 14.
    Wengst A, Reichl S (2010) RPMI 2650 epithelial model and three-dimensional reconstructed human nasal mucosa as in vitro models for nasal permeation studies. Eur J Pharm Biopharm 74:290–297PubMedCrossRefGoogle Scholar
  15. 15.
    Chen X, Cho DB, Yang PC (2010) Double staining immunohistochemistry. N Am J Med Sci 2:241–245PubMedGoogle Scholar
  16. 16.
    Cho SH, Oh SY, Zhu Z, Lee J, Lane AP (2012) Spontaneous eosinophilic nasal inflammation in a genetically-mutant mouse: comparative study with an allergic inflammation model. PLoS ONE 7:e35114PubMedCrossRefGoogle Scholar
  17. 17.
    Xie MQ, Liu J, Long Z, Tian DF, Zhao CQ, Yang PC (2011) Modulation of immune tolerance with a Chinese traditional prescription inhibits allergic rhinitis in mice. N Am J Med Sci 3:503–507PubMedCrossRefGoogle Scholar
  18. 18.
    Rondón C, Campo P, Herrera R, Blanca-Lopez N, Melendez L, Canto G, Torres MJ, Blanca M (2011) Nasal allergen provocation test with multiple aeroallergens detects polysensitization in local allergic rhinitis. J Allergy Clin Immunol 128:1192–1197PubMedCrossRefGoogle Scholar
  19. 19.
    Kim DW, Khalmuratova R, Hur DG, Jeon SY, Kim SW, Shin HW, Lee CH, Rhee CS (2011) Staphylococcus aureus enterotoxin B contributes to induction of nasal polypoid lesions in an allergic rhinosinusitis murine model. Am J Rhinol Allergy 25:255–261CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2012

Authors and Affiliations

  1. 1.Department of Otolaryngology & Head and Neck SurgeryFirst Hospital Affiliated Xiamen UniversityXiamenChina

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