Skip to main content
SpringerLink
Log in

IL-17C expression in nasal epithelial cells of chronic rhinosinusitis with nasal polyposis

  • Rhinology
  • Published:
European Archives of Oto-Rhino-Laryngology Aims and scope Submit manuscript

Abstract

Interleukin 17C (IL-17C) is a functionally distinct member of the IL-17 family that is selectively induced in epithelia by bacterial challenge and inflammatory stimuli. The goal of this study was to explore the expression of IL-17C in nasal epithelial cells and their role in the pathogenesis of chronic rhinosinusitis with nasal polyposis (CRSwNPs). IL-17C expression was detected using immunohistochemistry (IHC) of the epithelial cell layers and using the western blot assay on whole tissue homogenates from control subjects (n = 10) and CRSwNP patients [10 non-eosinophilic polyps and 10 eosinophilic polyps (EPs)]. Expression of IL-17C and P47-phox were evaluated in the human nasal epithelial cells (RPMI-2650 cells) after treatment with staphylococcal enterotoxin B (SEB) and pretreatment with reactive oxygen species (ROS) scavenger, N-acetyl l-cysteine (NAC). Finally, IL-17C expression was demonstrated in eosinophilic rhinosinusitis murine model using IHC. Epithelial expression of IL-17C was higher in nasal polyps (especially in EPs) compared to control mucosa. SEB increased the expression of IL-17C and P47-phox in RPMI-2650 cells. SEB-induced expressions of both IL-17C and P47-phox were significantly decreased in NAC-pretreated cells. Epithelial expression of IL-17C was significantly higher in experimental mice compared to control mice. SEB-induced IL-17C expression in nasal epithelial cells is mediated by ROS production. This pathway may be associated with the pathogenesis of CRSwNP, especially eosinophilic nasal polyps.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7

Similar content being viewed by others

References

  1. Fokkens WJ, Lund VJ, Mullol J et al (2012) European Position Paper on Rhinosinusitis and Nasal Polyps 2012. Rhinol Suppl 3p preceding table of contents, 1-298

  2. Corriveau MN, Zhang N, Holtappels G, Van Roy N, Bachert C (2009) Detection of Staphylococcus aureus in nasal tissue with peptide nucleic acid-fluorescence in situ hybridization. Am J Rhinol Allerg 23:461–465

    Article  Google Scholar 

  3. Sachse F, Becker K, von Eiff C, Metze D, Rudack C (2010) Staphylococcus aureus invades the epithelium in nasal polyposis and induces IL-6 in nasal epithelial cells in vitro. Allergy 65:1430–1437

    Article  CAS  PubMed  Google Scholar 

  4. Bernstein JM, Ballow M, Schlievert PM, Rich G, Allen C, Dryja D (2003) A superantigen hypothesis for the pathogenesis of chronic hyperplastic sinusitis with massive nasal polyposis. Am J Rhinol 17:321–326

    PubMed  Google Scholar 

  5. Van Zele T, Gevaert P, Watelet JB et al (2004) Staphylococcus aureus colonization and IgE antibody formation to enterotoxins is increased in nasal polyposis. J Allergy Clin Immunol 114:981–983

    Article  PubMed  CAS  Google Scholar 

  6. Yu RL, Dong Z (2009) Proinflammatory impact of Staphylococcus aureus enterotoxin B on human nasal epithelial cells and inhibition by dexamethasone. Am J Rhinol Allergy 23:15–20

    Article  PubMed  Google Scholar 

  7. O’Brien GJ, Riddell G, Elborn JS, Ennis M, Skibinski G (2006) Staphylococcus aureus enterotoxins induce IL-8 secretion by human nasal epithelial cells. Respir Res 7:115

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  8. Huvenne W, Callebaut I, Reekmans K et al (2010) Staphylococcus aureus enterotoxin B augments granulocyte migration and survival via airway epithelial cell activation. Allergy 65:1013–1020

    Article  CAS  PubMed  Google Scholar 

  9. Kim DW, Khalmuratova R, Hur DG et al (2011) Staphylococcus aureus enterotoxin B contributes to induction of nasal polypoid lesions in an allergic rhinosinusitis murine model. Am J Rhinol Allerg 25:e255–e261

    Article  Google Scholar 

  10. Chang SH, Reynolds JM, Pappu BP, Chen G, Martinez GJ, Dong C (2011) Interleukin-17C promotes Th17 cell responses and autoimmune disease via interleukin-17 receptor E. Immunity 35:611–621

    Article  CAS  PubMed  Google Scholar 

  11. Gaffen SL (2009) Structure and signalling in the IL-17 receptor family. Nat Rev Immunol 9:556–567

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Pfeifer P, Voss M, Wonnenberg B et al (2013) IL-17C is a mediator of respiratory epithelial innate immune response. Am J Respir Cell Mol Biol 48:415–421

    Article  CAS  PubMed  Google Scholar 

  13. Ramirez-Carrozzi V, Sambandam A, Luis E et al (2011) IL-17C regulates the innate immune function of epithelial cells in an autocrine manner. Nat Immunol 12:1159–1166

    Article  CAS  PubMed  Google Scholar 

  14. Im E, Jung J, Rhee SH (2012) Toll-like receptor 5 engagement induces interleukin-17C expression in intestinal epithelial cells. J Interferon Cytokine Res 32:583–591

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Johnston A, Fritz Y, Dawes SM et al (2013) Keratinocyte overexpression of IL-17C promotes psoriasiform skin inflammation. J Immunol 190:2252–2262

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Cao PP, Li HB, Wang BF et al (2009) Distinct immunopathologic characteristics of various types of chronic rhinosinusitis in adult Chinese. J Allerg Clin Immunol 124:478–484 e471–472

    Article  CAS  Google Scholar 

  17. Boldogh I, Bacsi A, Choudhury BK et al (2005) ROS generated by pollen NADPH oxidase provide a signal that augments antigen-induced allergic airway inflammation. J Clin Invest 115:2169–2179

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Kedzierska A, Kaszuba-Zwoinska J, Slodowska-Hajduk Z et al (2005) SEB-induced T cell apoptosis in atopic patients–correlation to clinical status and skin colonization by Staphylococcus aureus. Arch Immunol Ther Exp (Warsz) 53:63–70

    CAS  Google Scholar 

  19. Uneri C, Ozturk O, Polat S, Yuksel M, Haklar G (2005) Determination of reactive oxygen species in nasal polyps. Rhinology 43:185–189

    PubMed  Google Scholar 

  20. Krakauer T (2010) Therapeutic down-modulators of staphylococcal superantigen-induced inflammation and toxic shock. Toxins (Basel) 2:1963–1983

    Article  CAS  Google Scholar 

  21. Grote K, Flach I, Luchtefeld M et al (2003) Mechanical stretch enhances mRNA expression and proenzyme release of matrix metalloproteinase-2 (MMP-2) via NAD(P)H oxidase-derived reactive oxygen species. Circ Res 92:e80–e86

    Article  CAS  PubMed  Google Scholar 

  22. Xiao C, Puddicombe SM, Field S et al (2011) Defective epithelial barrier function in asthma. J Allerg Clin Immunol 128:549–556 e541–512

    Article  CAS  Google Scholar 

  23. Beisswenger C, Lysenko ES, Weiser JN (2009) Early bacterial colonization induces toll-like receptor-dependent transforming growth factor beta signaling in the epithelium. Infect Immun 77:2212–2220

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Jeanson L, Kelly M, Coste A et al (2012) Oxidative stress induces unfolding protein response and inflammation in nasal polyposis. Allergy 67:403–412

    Article  CAS  PubMed  Google Scholar 

  25. Segal BH, Han W, Bushey JJ et al (2010) NADPH oxidase limits innate immune responses in the lungs in mice. PLoS One 5:e9631

    Article  PubMed  PubMed Central  CAS  Google Scholar 

Download references

Acknowledgments

We thank the study participants and all joint research workers. We also thank the patients who provided samples for the study.

This research was supported by the Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science and Technology (2011-0009790).

Conflict of interest

No potential conflict of interest relevant to this article was reported.

Author information

Authors and Affiliations

  1. Department of Otorhinolaryngology-Head and Neck Surgery, Research Institute for Medical Science, Chungnam National University School of Medicine, 282 Munhwa-ro Jung-gu, Daejeon, 301-721, Korea

    Jun Jin, Ki-Sang Rha & Yong Min Kim

  2. Department of Anatomy, Brain Research Institute, Chungnam National University School of Medicine, Daejeon, Korea

    Dong Woon Kim

  3. Yanbian University Hospital, Jilin Yanji, China

    Jun Jin

Authors
  1. Jun Jin
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Ki-Sang Rha
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Dong Woon Kim
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Yong Min Kim
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Yong Min Kim.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Jin, J., Rha, KS., Kim, D.W. et al. IL-17C expression in nasal epithelial cells of chronic rhinosinusitis with nasal polyposis. Eur Arch Otorhinolaryngol 271, 1097–1105 (2014). https://doi.org/10.1007/s00405-013-2683-x

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00405-013-2683-x

Keywords

Search

Navigation