Expression Profile of Six RNA-Binding Proteins in Pulmonary Sarcoidosis

<div><p>Background</p><p>Sarcoidosis is characterised by up-regulation of cytokines and chemokine ligands/receptors and proteolytic enzymes. This pro-inflammatory profile is regulated post-transcriptionally by RNA-binding proteins (RBPs). We investigated <i>in vivo</i> expression of six RBPs (AUF1, HuR, NCL, TIA, TIAR, PCBP2) and two inhibitors of proteolytic enzymes (RECK, PTEN) in pulmonary sarcoidosis and compared it to the expression in four control groups of healthy individuals and patients with other respiratory diseases: chronic obstructive pulmonary disease (COPD), asthma and idiopathic interstitial pneumonias (IIPs).</p><p>Methods</p><p>RT-PCR was used to quantify the mRNAs in bronchoalveolar (BA) cells obtained from 50 sarcoidosis patients, 23 healthy controls, 30 COPD, 19 asthmatic and 19 IIPs patients. Flow cytometry was used to assess intracellular protein expression of AUF1 and HuR in peripheral blood T lymphocytes (PBTLs) obtained from 9 sarcoidosis patients and 6 healthy controls.</p><p>Results</p><p>Taking the stringent conditions for multiple comparisons into consideration, we consistently observed in the primary analysis including all patients regardless of smoking status as well as in the subsequent sub-analysis limited for never smokers that the BA mRNA expression of AUF1 (<i>p</i><0.001), TIA (<i>p</i><0.001), NCL (<i>p</i><0.01) and RECK (<i>p</i><0.05) was decreased in sarcoidosis compared to healthy controls. TIA mRNA was also decreased in sarcoidosis compared to both obstructive pulmonary diseases (COPD and asthma; <i>p</i><0.001) but not compared to IIPs. There were several positive correlations between RECK mRNA and RBP mRNAs in BA cells. Also sarcoidosis CD3+, CD4+ and CD8+ PBTLs displayed lower mean fluorescence intensity of AUF1 (<i>p≤</i>0.02) and HuR (<i>p≤</i>0.03) proteins than control healthy PBTLs.</p><p>Conclusion</p><p>mRNA expressions of three RBPs (AUF1, TIA and NCL) and their potential target mRNA encoding RECK in BA cells and additionally protein expression of AUF1 and HuR in PBTLs were down-regulated in our sarcoidosis patients compared to healthy individuals. Its significance, e.g. for stability of mRNAs encoding pro-inflammatory factors, should be further explored in sarcoidosis.</p></div

PSMB2 and RPL32 are suitable denominators to normalize gene expression profiles in bronchoalveolar cells-2

Zed to 1); the whiskers on each box represent the SD values. For details see Methods section Gene expression measurements by qRT-PCR. *< 0.05.<p><b>Copyright information:</b></p><p>Taken from "PSMB2 and RPL32 are suitable denominators to normalize gene expression profiles in bronchoalveolar cells"</p><p>http://www.biomedcentral.com/1471-2199/9/69</p><p>BMC Molecular Biology 2008;9():69-69.</p><p>Published online 31 Jul 2008</p><p>PMCID:PMC2529339.</p><p></p

Use of ICS in monotherapy or combination therapy.

<p>Use of ICS in monotherapy or combination therapy.</p

PSMB2 and RPL32 are suitable denominators to normalize gene expression profiles in bronchoalveolar cells-1

Ents with involvement of parenchyma: CXR stages II/III)-Mean(patients without involvement of parenchyma: CXR stage I), Mean(Löfgren's syndrome patients)-Mean(non-Löfgren's syndrome patients), Mean(multi-organ involvement)-Mean(involvement of lung only), Mean(smokers)-Mean(non-smokers), Mean(males)-Mean(females), and Mean(pathological BAL cell count)-Mean(normal BAL cell count) for macrophages, lymphocytes, neutrophils and eosinophils. For more details see the legend to Fig. 2.<p><b>Copyright information:</b></p><p>Taken from "PSMB2 and RPL32 are suitable denominators to normalize gene expression profiles in bronchoalveolar cells"</p><p>http://www.biomedcentral.com/1471-2199/9/69</p><p>BMC Molecular Biology 2008;9():69-69.</p><p>Published online 31 Jul 2008</p><p>PMCID:PMC2529339.</p><p></p

Effect of number of COPD patients seen in a month on a discrepancy between subjectively classified patients into GOLD 2011 groups and classification achieved by objective assessment using software.

<p>Effect of number of COPD patients seen in a month on a discrepancy between subjectively classified patients into GOLD 2011 groups and classification achieved by objective assessment using software.</p

Contribution to the misclassification of an individual clinical component interpreted within the GOLD 2011 classification matrix.

<p>The percentage indicates relative frequency of misclassified cases attributable to a given clinical component. A sole effect is responsible for misclassified cases due to an obvious error in interpretation of one specific primary clinical parameter. The combined effect is responsible for misclassified cases due to an obvious error in interpreting both clinical criteria on the same axis (mMRC dyspnea scale and CAT respective bronchial obstruction and number of COPD exacerbations/year). <i>Statistical probabilities were calculated of pair-wise contrasts as follows; mMRC dyspnea scale vs. CAT (p>0.05), mMRC dyspnea scale vs. bronchial obstruction based on post bronchodilator FEV1 (p<0.0001), mMRC dyspnea scale vs. number of exacerbations/year (p<0.0001), CAT vs. bronchial obstruction (p<0.0001), CAT vs. number of exacerbations/year (p<0.0001), bronchial obstruction vs. number of exacerbations/year (p<0.0001).</i></p

Original version of the Czech Republic map in SVG format.

<p>Original version of the Czech Republic map in SVG format.</p

Numbers of COPD specialists involved in the research by country regions of the Czech Republic.

<p>Numbers of COPD specialists involved in the research by country regions of the Czech Republic.</p

PSMB2 and RPL32 are suitable denominators to normalize gene expression profiles in bronchoalveolar cells-0

Ker box plots; the box represents the 25th–75th percentiles, the median is indicated by a bar across the box, the whiskers on each box represent the minimum and maximum values.<p><b>Copyright information:</b></p><p>Taken from "PSMB2 and RPL32 are suitable denominators to normalize gene expression profiles in bronchoalveolar cells"</p><p>http://www.biomedcentral.com/1471-2199/9/69</p><p>BMC Molecular Biology 2008;9():69-69.</p><p>Published online 31 Jul 2008</p><p>PMCID:PMC2529339.</p><p></p