Advances in Clinical and Experimental Medicine

Title abbreviation: Adv Clin Exp Med
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ISSN 1899–5276 (print)
ISSN 2451-2680 (online)
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Advances in Clinical and Experimental Medicine

2013, vol. 22, nr 2, March-April, p. 209–217

Publication type: original article

Language: English

Microarray Analysis of NF-κB-dependent Genes in Chronic Rhinosinusitis with Nasal Polyps

Analiza profilu ekspresji genów zależnych od czynnika transkrypcyjnego NF-κB w przewlekłym zapaleniu zatok przynosowych z polipami

Marcin Frączek1,C,D,F, Beata Rostkowska-Nadolska1,A,B,C,E, Małgorzata Kapral2,A,B,C, Justyna Szota3,B,E, Tomasz Kręcicki1,E, Urszula Mazurek3,A,C,E

1 Department of Otolaryngology, Wroclaw Medical University, Poland

2 Department of Biochemistry, Medical University of Silesia, Sosnowiec, Poland

3 Department of Molecular Biology, Medical University of Silesia, Sosnowiec, Poland

Abstract

Background. The inflammatory process underlying nasal polyposis is induced and perpetuated by the enhanced activity of several agents including transcription factors. It has recently been demonstrated that one of them, named nuclear factor-kappa B (NF-κB), is implicated in the regulation of multiple pro-inflammatory genes.
Objectives. The aim of the study was to identify using microarray technology which NF-κB-dependent genes are activated in nasal polyp (NP) samples compared to the control mucosa.
Material and Methods. The transcriptional activity of genes was analyzed using an oligonucleotide microarray on 15 NPs and 8 cases of normal nasal mucosa.
Results. Gene expression patterns obtained in NPs were significantly different from those in normal mucosa. NPs and control cases clustered separately, each of them with large homogeneity in gene expression. Among 582 human NF-κB-dependent genes 25 showed a significantly higher expression in NPs compared to the control. The largest increase focused on gene encoding TFF3 (a 5-fold higher expression) followed by NOS2A (5x), SERPINA1 (4x), UCP2 (4x), OXTR (4x) and IL8 (3x) (p < 0.05). In healthy mucosa 19 genes presented increased transcription activity compared to NPs. The most significantly enhanced levels were shown in case of LTF gene (20 fold) followed by KRT6B (7x), LYZ (7x), SD11B2 (5x) and MMP3 (4x) (p < 0.05).
Conclusion. DNA microarray technology highlights the involvement of many unsuspected pathologic pathways which could be involved in NP growth. The identification of novel disease-related genes may help to understand the biology of NPs and elaborate new targeted therapy.

Streszczenie

Wprowadzenie.W złożonej etiologii przewlekłego zapalenia zatok przynosowych z polipami (PZZPzP) istotną rolę pełni zwiększona aktywność niektórych czynników transkrypcyjnych. Jednym z nich jest czynnik transkrypcji jądrowej NF kappa B (NF-κB), który reguluje ekspresję wielu genów kodujących białka o właściwościach prozapalnych.
Cel pracy. Ocena profilu ekspresji genów zależnych od aktywności NF-κB w PZZPzP w porównaniu z niezmienioną błoną śluzową jamy nosa osób z wykluczonym procesem zapalnym.
Materiał i metody. Aktywność transkrypcyjna genów została oceniona metodą mikromacierzy oligonukleotydowych w grupie 15 pacjentów z PZZPzP i w 8-osobowej grupie kontrolnej.
Wyniki. Profil ekspresji genów w PZZPzP różnił się istotnie w porównaniu z profilem w niezmienionej błonie śluzowej jamy nosa. Analiza skupień wyróżniła dwie oddzielne grupy pacjentów (z PZZPzP oraz grupę kontrolną). Obie charakteryzowały się dużą jednorodnością ekspresji genów. Spośród 582 genów zależnych od czynnika transkrypcyjnego NF-κB 25 miało istotnie zwiększoną ekspresję w PZZPzP w porównaniu z grupą kontrolną. Były to geny kodujące białka: TFF3 (5x większa ekspresja), NOS2A (5x), SERPINA1 (4x), UCP2 (4x), OXTR (4x) i Il8 (3x) (p < 0.05). W grupie kontrolnej 19 genów charakteryzowała zwiększona ekspresja w stosunku do grup z PZZPzP. Największą różnicę ekspresji wykazały geny: LTF (20x większa ekspresja), KRT6B (7x), LYZ (7x), SD11B2 (5x) i MMP3 (4x) (p < 0.05).
Wnioski. Analizowanie profilu ekspresji genów z użyciem mikromacierzy oligonukleotydowych sugeruje istnienie niezbadanych dotąd szlaków patologicznych, które mogą mieć znaczenie w etiologii PZZPzP. Identyfikacja nowych genów związanych z PZZP może pomóc w zrozumieniu biologii tego schorzenia, a w przyszłości opracowaniu nowej celowanej terapii.

Key words

chronic rhinosinusitis, nasal polyps, DNA microarray, NF-κB.

Słowa kluczowe

zapalenie zatok przynosowych, polipy nosa, mikromacierze DNA, NF-κB.

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