Transcriptional activity of genes-encoding kinin B1 and B2 receptors and kinin-dependent genes in nasal polyps

Abstract

The pro-inflammatory effects of kinins are mediated by two bradykinin receptors: BR1 and BR2. The aim of this study was to evaluate the expression profile of kinin receptor genes by an estimation of mRNA levels in human nasal polyps (NP) and normal mucosa (NM). BR1 and BR2-dependent genes differentially transcribed in NP were investigated using oligonucleotide microarray technology. The mRNA copy number of BR1, BR2 and TIMP1 genes was assessed by QRT-PCR. Thirty six eosinophilic (ENP), 17 neutrophilic nasal polyps (NNP) and 28 NM samples were included into the study. Among 92 genes encoding proteins involved in signal transduction via B1 and B2 kinin receptors TIMP1 was found to be 2,63-fold higher in the NP than in NM. Increased TIMP1 gene expression was proved by QRT-PCR (p=0,003). Moreover two genes: FOS and PTGS1 presented higher (3,82- and 4,27-fold, respectively) expression in NM compared to NP tissues. In QRT-PCR analysis insignificantly higher expression of gene encoding BR1 in ENP [2564 mRNA copies/microg RNA (22-32863)] compared with NM [1426 copies mRNA (15-27995)] was found. mRNA expression for the BR2 in ENP [9872 copies mRNA (19-244832)] was insignificantly higher than in NM [5753 copies (46-199658)]. BR2 mRNA was the predominant transcript in most NP and NM samples followed by BR1 mRNA (p<0,01). There was a positive correlation between the expression of BR1 and BR2 in the ENP (r=0,91; p<0,01) and NNP (r=0,6; p<0,01). We did not document any changes in the expression profile of kinin receptors in the analyzed groups, which may suggest that kinin receptors do not make an important contribution in the etiology of NP.