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Increased gene expression of inflammatory markers in nasal turbinate of patients with persistent allergic rhinitis and chronic obstruction

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Abstract

Purpose

The pathogenesis of persistent allergic rhinitis with chronic and refractory nasal obstruction is still unknown. Inflammation and tissue remodeling are known to play a role, but this has not been studied thoroughly. The purpose of this study is to identify the profile of gene expression of inflammatory and remodeling markers in nasal mucosa of patients with PAR and chronic obstruction.

Methods

After informed consent, we obtained nasal mucosa tissue from five aeroallergen-sensitized PAR patients undergoing anterior turbinectomy, and control non-sensitized individuals undergoing cerebrospinal fluid fistula repair or rhinoplasty. We assessed the expression of 34 genes related to inflammation and tissue remodeling using the real-time polymerase chain reaction (qPCR) to quantify each mRNA.

Results

IL-4 mRNA was upregulated in nasal mucosa of all five patients; CCR3, CCR8 and Eotaxin-2 were upregulated in four out of five patient samples; while IL-5 and IL-13 were upregulated in two of them. TGF-β1 was not upregulated in PAR samples. mRNA from metalloproteinases MMP-7, MMP13 and MMP15 were upregulated in three out of five samples. Our results indicate a typical mRNA expression profile of the infiltrating inflammatory Th2 cells and eosinophils, combined with altered gene expression of remodeling-related proteins in stromal cells from the mucosa.

Conclusion

Prolonged allergen challenge can lead to persistent upregulation of genes for inflammatory mediators such as IL-4 Th2/eosinophil cytokines, chemokines and receptors, which may play an important role in maintaining PAR with chronic nasal obstruction. Our findings may have therapeutic implications, including the use of anti-IL4, -CCR3 or -MMP therapy to ameliorate the condition.

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Funding

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP, Brazil) Grant number 04/08488-3.

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Authors and Affiliations

  1. Division of Clinical Immunology and Allergy, Department of Medicine, Faculdade de Medicina FMUSP, Universidade de Sao Paulo, Av. Dr. Arnaldo, 455 s. 3207, Sao Paulo, SP, 01246-000, Brazil

    Lucila de Campos, Clóvis Eduardo Santos Galvão, Jorge Kalil, Fábio Morato Castro & Edécio Cunha-Neto

  2. Laboratory of Immunology, Instituto do Coração (Incor) Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de Sao Paulo, São Paulo, SP, Brazil

    Eliane Conti Mairena, Jorge Kalil & Edécio Cunha-Neto

  3. Division of Otorhinolaryngology, Faculdade de Medicina FMUSP, Universidade de Sao Paulo, São Paulo, SP, Brazil

    Richard Voegels

  4. Institute of Investigation in Immunology (iii), INCT, São Paulo, Brazil

    Jorge Kalil, Fábio Morato Castro & Edécio Cunha-Neto

Authors
  1. Lucila de Campos
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  2. Clóvis Eduardo Santos Galvão
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  3. Eliane Conti Mairena
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  4. Richard Voegels
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  5. Jorge Kalil
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  6. Fábio Morato Castro
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  7. Edécio Cunha-Neto
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Corresponding author

Correspondence to Edécio Cunha-Neto.

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Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the University of São Paulo School of Medicine ethics committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

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Informed consent was obtained from all individual participants included in the study.

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de Campos, L., Galvão, C.E.S., Mairena, E.C. et al. Increased gene expression of inflammatory markers in nasal turbinate of patients with persistent allergic rhinitis and chronic obstruction. Eur Arch Otorhinolaryngol 276, 3247–3249 (2019). https://doi.org/10.1007/s00405-019-05581-8

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  • DOI: https://doi.org/10.1007/s00405-019-05581-8

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