title: Expression Profile of Six RNA-Binding Proteins in Pulmonary Sarcoidosis.
abstract: BACKGROUND
  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 in vivo 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).
  
  
  METHODS
  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.
  
  
  RESULTS
  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 (p<0.001), TIA (p<0.001), NCL (p<0.01) and RECK (p<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; p<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 (p≤0.02) and HuR (p≤0.03) proteins than control healthy PBTLs.
  
  
  CONCLUSIONS
  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.
authors: Laboratory of Immunogenomics and Immunoproteomics, Department of Pathological Physiology, Faculty of Medicine and Dentistry Palacky University, Olomouc, Czech Republic.|Respiratory Medicine Unit, Department of Medicine, Karolinska Institutet, Stockholm, Sweden.|Institute of Molecular and Translational Medicine, Faculty of Medicine and Dentistry, Palacky University, Olomouc, Czech Republic.
authors: Zdenka
authors: http://orcid.org/0000-0002-7983-3333
authors: Z
authors: Navratilova
authors: Laboratory of Immunogenomics and Immunoproteomics, Department of Pathological Physiology, Faculty of Medicine and Dentistry Palacky University, Olomouc, Czech Republic.
authors: Eva
authors: E
authors: Novosadova
authors: Respiratory Medicine Unit, Department of Medicine, Solna & Center for Molecular Medicine, Karolinska Institutet, Stockholm, Sweden.
authors: Michael
authors: M
authors: Hagemann-Jensen
authors: Respiratory Medicine Unit, Department of Medicine, Karolinska Institutet, Stockholm, Sweden.
authors: Susanna
authors: S
authors: Kullberg
authors: Department of Respiratory Medicine, Palacky University, Olomouc, Czech Republic.
authors: Vitezslav
authors: V
authors: Kolek
authors: Respiratory Medicine Unit, Department of Medicine, Karolinska Institutet, Stockholm, Sweden.
authors: Johan
authors: J
authors: Grunewald
authors: Laboratory of Immunogenomics and Immunoproteomics, Department of Pathological Physiology, Faculty of Medicine and Dentistry Palacky University, Olomouc, Czech Republic.|Institute of Molecular and Translational Medicine, Faculty of Medicine and Dentistry, Palacky University, Olomouc, Czech Republic.
authors: Martin
authors: M
authors: Petrek
mesh_terms: D000328:Adult; D000368:Aged; D001249:Asthma / Q000235:genetics* / Q000378:metabolism; D000067780:ELAV-Like Protein 1 / Q000235:genetics / Q000378:metabolism; D005260:Female; D058851:GPI-Linked Proteins / Q000235:genetics / Q000378:metabolism; D020869:Gene Expression Profiling / Q000379:methods*; D005786:Gene Expression Regulation; D000081035:Heterogeneous Nuclear Ribonucleoprotein D0; D034502:Heterogeneous-Nuclear Ribonucleoprotein D / Q000235:genetics / Q000378:metabolism; D006801:Humans; D054988:Idiopathic Interstitial Pneumonias / Q000235:genetics* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D051059:PTEN Phosphohydrolase / Q000235:genetics / Q000378:metabolism; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism; D039102:Poly(A)-Binding Proteins / Q000235:genetics / Q000378:metabolism; D029424:Pulmonary Disease, Chronic Obstructive / Q000235:genetics* / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D017565:Sarcoidosis, Pulmonary / Q000235:genetics* / Q000378:metabolism; D000074019:T-Cell Intracellular Antigen-1; D013601:T-Lymphocytes / Q000378:metabolism; D055815:Young Adult; D000097796:Nucleolin
chemical_list: D000067780:ELAV-Like Protein 1; D058851:GPI-Linked Proteins; D000081035:Heterogeneous Nuclear Ribonucleoprotein D0; D034502:Heterogeneous-Nuclear Ribonucleoprotein D; D051059:PTEN Phosphohydrolase; D010750:Phosphoproteins; D039102:Poly(A)-Binding Proteins; D016601:RNA-Binding Proteins; D000074019:T-Cell Intracellular Antigen-1; D000097796:Nucleolin; C098770:ELAVL1 protein, human; C000630986:HNRNPD protein, human; C501903:PCBP2 protein, human; C115460:RECK protein, human; C071558:TIA1 protein, human; C076751:TIAL1 protein, human; C494929:PTEN protein, human