title: Deleted in malignant brain tumors 1 (DMBT1) elicits increased VEGF and decreased IL-6 production in type II lung epithelial cells.
abstract: BACKGROUND
  Deleted in malignant brain tumors 1 (DMBT1) is an innate defence protein expressed in the lungs of preterm infants and adults. Recent studies showed that DMBT1 is important in angiogenesis and can bind to different growth factors including VEGF. We aimed at examining relationships between VEGF and IL-6 levels to DMBT1 expression in the lungs of preterm and term infants and in lung epithelial cells in vitro.
  
  
  METHODS
  We examined by ELISA VEGF levels in 120 tracheal aspirates of 57 preterm and term infants and tested for correlation with different perinatal factors as well as with DMBT1 levels. To examine the effect of DMBT1 on VEGF and IL-6 expression we compared type II lung epithelial A549 cells stably transfected with a DMBT1 expression plasmid (DMBT1+ cells) to A549 cells stably transfected with an empty expression plasmid (DMBT1- cells). The concentrations of VEGF and IL-6 were determined via ELISA in the supernatant of the unstimulated cells and after stimulation with LPS, TNFα and Phorbol-12-myristate-13-acetate (PMA).
  
  
  RESULTS
  The VEGF levels in the tracheal aspirates of preterm and term infants were significantly correlated with DMBT1 levels (p = 0.0032), the postnatal age (p = 0.0073) and the presence of neonatal infection/sepsis (p = 0.0002). Unstimulated DMBT1+ A549 cells showed significantly higher VEGF expression (p = 0.0017) than DMBT1- cells. Significantly elevated VEGF levels were also confirmed for DMBT1+ cells after stimulation with TNFα (p = 0.0008), LPS (p = 0.0232) and PMA (p = 0.0025). The IL-6 levels were comparable in DMBT1+ versus DMBT1- cells without stimulation (p = 0.6028), but they were significantly reduced in DMBT1+ cells after stimulation with TNFα (p = 0.0003), LPS (p = 0.0088) and PMA (p = 0.0039).
  
  
  CONCLUSIONS
  The data indicate that DMBT1 promotes VEGF and suppresses IL-6 production in alveolar tissues, which could point to DMBT1 having a possible role in the transition from inflammation to regeneration and being a potentially useful clinical marker.
authors.affiliation: Department of Pediatrics I, Neonatology, University Hospital Essen, University Duisburg-Essen, Hufelandstr. 55, 45147, Essen, Germany. Hanna.Mueller@uk-essen.de.|Division of Neonatology, Department of Pediatrics, University of Heidelberg, Im Neuenheimer Feld 430, 69120, Heidelberg, Germany. Hanna.Mueller@uk-essen.de.
authors.forename: Hanna
authors.initials: H
authors.lastname: Müller
authors.affiliation: Division of Neonatology, Department of Pediatrics, University of Heidelberg, Im Neuenheimer Feld 430, 69120, Heidelberg, Germany. nagel_christian@hotmail.com.
authors.forename: Christian
authors.initials: C
authors.lastname: Nagel
authors.affiliation: Institute of Medical Statistics and Biomathematics, University Hospital Mannheim, Ludolf-Krehl-Straße 13-17D, 68167, Mannheim, Germany. christel.weiss@medma.uni-heidelberg.de.
authors.forename: Christel
authors.initials: C
authors.lastname: Weiss
authors.affiliation: Molecular Oncology and Lundbeckfonden Center of Excellence NanoCAN, Institute for Molecular Medicine, University of Southern Denmark, JB Winsloews Vej 25, 5000, Odense C, Denmark. jmollenhauer@health.sdu.dk.
authors.forename: Jan
authors.initials: J
authors.lastname: Mollenhauer
authors.affiliation: Division of Neonatology, Department of Pediatrics, University of Heidelberg, Im Neuenheimer Feld 430, 69120, Heidelberg, Germany. Johannes.Poeschl@med.uni-heidelberg.de.
authors.forename: Johannes
authors.initials: J
authors.lastname: Poeschl
mesh_terms: D002135:Calcium-Binding Proteins; D002273:Carcinogens / Q000494:pharmacology; D016022:Case-Control Studies; D045744:Cell Line, Tumor; D004268:DNA-Binding Proteins; D004797:Enzyme-Linked Immunosorbent Assay; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D066298:In Vitro Techniques; D007231:Infant, Newborn; D007234:Infant, Premature; D015850:Interleukin-6 / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000494:pharmacology; D008168:Lung / Q000166:cytology / Q000378:metabolism*; D011956:Receptors, Cell Surface / Q000378:metabolism*; D012127:Respiratory Distress Syndrome, Newborn / Q000378:metabolism*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D025521:Tumor Suppressor Proteins; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism*
chemical_list: D002135:Calcium-Binding Proteins; D002273:Carcinogens; C108174:DMBT1 protein, human; D004268:DNA-Binding Proteins; C508600:IL6 protein, human; D015850:Interleukin-6; D008070:Lipopolysaccharides; D011956:Receptors, Cell Surface; D014409:Tumor Necrosis Factor-alpha; D025521:Tumor Suppressor Proteins; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D013755:Tetradecanoylphorbol Acetate