Gene expression differences in nitric oxide and reactive oxygen species regulation point to an altered innate immune response in chronic rhinosinusitis

Authors

  • Camille Jardeleza MD,

    1. Department of Surgery, Otorhinolaryngology–Head and Neck Surgery, The Queen Elizabeth Hospital and the University of Adelaide, Adelaide, South Australia, Australia
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  • Damien Jones Bsc,

    1. Department of Surgery, Otorhinolaryngology–Head and Neck Surgery, The Queen Elizabeth Hospital and the University of Adelaide, Adelaide, South Australia, Australia
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  • Leonie Baker BSc (Hons),

    1. Department of Surgery, Otorhinolaryngology–Head and Neck Surgery, The Queen Elizabeth Hospital and the University of Adelaide, Adelaide, South Australia, Australia
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  • Dijana Miljkovic BBtech,

    1. Department of Surgery, Otorhinolaryngology–Head and Neck Surgery, The Queen Elizabeth Hospital and the University of Adelaide, Adelaide, South Australia, Australia
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  • Samuel Boase BMBS (Hons),

    1. Department of Surgery, Otorhinolaryngology–Head and Neck Surgery, The Queen Elizabeth Hospital and the University of Adelaide, Adelaide, South Australia, Australia
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  • Neil Cheng-Wen Tan MBBS,

    1. Department of Surgery, Otorhinolaryngology–Head and Neck Surgery, The Queen Elizabeth Hospital and the University of Adelaide, Adelaide, South Australia, Australia
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  • Sarah Vreugde MD,

    1. Department of Surgery, Otorhinolaryngology–Head and Neck Surgery, The Queen Elizabeth Hospital and the University of Adelaide, Adelaide, South Australia, Australia
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  • Lor Wai Tan PhD,

    1. Department of Surgery, Otorhinolaryngology–Head and Neck Surgery, The Queen Elizabeth Hospital and the University of Adelaide, Adelaide, South Australia, Australia
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  • Peter-John Wormald MD

    Corresponding author
    • Department of Surgery, Otorhinolaryngology–Head and Neck Surgery, The Queen Elizabeth Hospital and the University of Adelaide, Adelaide, South Australia, Australia
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  • Funding sources for the study: The Garnett Passe and Rodney Williams Memorial Foundation and The University of Adelaide, Faculty of Health Science, Adelaide, South Australia.

  • Potential conflict of interest: P.J.W. receives royalties from Medtronic for instruments designed and is a consultant for Neilmed Pty Ltd., but this is not relevant to this study.

  • Presented orally at the Annual ARS Meeting on September 8, 2012, Washington, DC.

Correspondence to: Peter-John Wormald, MD, Department of Otorhinolaryngology–Head and Neck Surgery, The Queen Elizabeth Hospital, 28 Woodville Rd, Woodville South, South Australia 5011, Australia; e-mail: peterj.wormald@adelaide.edu.au

Abstract

Background

The complex interplay between host, environment, and microbe in the etiopathogenesis of chronic rhinosinusitis (CRS) remains unclear. This study focuses on the host-microbe interaction, specifically the regulation of nitric oxide (NO) and reactive oxygen species (ROS) against the pathogenic organism Staphylococcus aureus (S. aureus). NO and ROS play crucial roles in innate immunity and in the first-line defense against microbial invasion.

Methods

Sinonasal tissue samples were harvested from CRS and control patients during surgery. CRS patients were classified S. aureus biofilm-positive (B+) or biofilm-negative (B−) using fluorescence in situ hybridization and clinically as polyp-positive (P+) or polyp-negative (P−). Samples were assessed using an NO polymerase chain reaction (PCR) array containing 84 genes involved in NO and ROS regulation, and gene expression of all subgroups were compared to each other.

Results

Twenty-three samples were analyzed with 31 genes significantly changed, the greatest seen in the B+P+ CRS patients. Four genes consistently displayed differential expression between the groups including the cytoprotective oxidation resistance 1 (OXR1) and peroxiredoxin 6 (PRDX6), neutrophil cytosolic factor 2 (NCF2), and the prion protein (PRNP) genes.

Conclusion

Alteration in gene expression points to impaired innate immune responses differing among CRS subgroups based on S. aureus biofilm and polyp status. The consistent alteration of 4 genes among distinct groups demonstrates that S. aureus biofilms and polyps are associated with specific changes in gene expression. Further studies are required to validate these findings in a wider cohort of patients and correlate this to protein expression and disease manifestation.

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