title: Microarray analysis revealing common and distinct functions of promyelocytic leukemia protein (PML) and tumor necrosis factor alpha (TNFα) signaling in endothelial cells.
abstract: BACKGROUND
  Promyelocytic leukemia protein (PML) is a tumor suppressor that is highly expressed in endothelial cells nonetheless its role in endothelial cell biology remains elusive. Tumor necrosis factor alpha (TNFα) is an important cytokine associated with many inflammation-related diseases. We have previously demonstrated that TNFα induces PML protein accumulation. We hypothesized that PML may play a role in TNFα signaling pathway. To identify potential PML target genes and investigate the putative crosstalk between PML's function and TNFα signaling in endothelial cells, we carried out a microarray analysis in human primary umbilical endothelial cells (HUVECs).
  
  
  RESULTS
  We found that PML and TNFα regulate common and distinct genes involved in a similar spectrum of biological processes, pathways and human diseases. More importantly, we found that PML is required for fine-tuning of TNFα-mediated immune and inflammatory responses. Furthermore, our data suggest that PML and TNFα synergistically regulate cell adhesion by engaging multiple molecular mechanisms. Our biological functional assays exemplified that adhesion of U937 human leukocytes to HUVECs is co-regulated by PML and TNFα signaling.
  
  
  CONCLUSIONS
  Together, our study identified PML as an essential regulator of TNFα signaling by revealing the crosstalk between PML knockdown-mediated effects and TNFα-elicited signaling, thereby providing novel insights into TNFα signaling in endothelial cells.
authors.affiliation: Department of Biochemistry, School of Medicine, Case Western Reserve University (CWRU) and the Comprehensive Cancer Center of CWRU and University Hospital of Cleveland (UHC), Cleveland, OH 44106, USA.
authors.forename: Xiwen
authors.initials: X
authors.lastname: Cheng
authors.forename: Hung-Ying
authors.initials: HY
authors.lastname: Kao
mesh_terms: D002448:Cell Adhesion / Q000235:genetics; D005786:Gene Expression Regulation / Q000235:genetics*; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D046228:Microarray Analysis; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D000071156:Promyelocytic Leukemia Protein; D015398:Signal Transduction / Q000235:genetics*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism*; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism*; D020298:U937 Cells
chemical_list: D009687:Nuclear Proteins; D000071156:Promyelocytic Leukemia Protein; D014157:Transcription Factors; D014409:Tumor Necrosis Factor-alpha; D025521:Tumor Suppressor Proteins; C070576:PML protein, human