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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 (TNF α ) is an important cytokine associated with many inflammation-related diseases. We have previously demonstrated that TNF α  induces PML protein accumulation. We hypothesized that PML may play a role in TNF α  signaling pathway. To identify potential PML target genes and investigate the putative crosstalk between PML’s function and TNF α  signaling in endothelial cells, we carried out a microarray analysis in human primary umbilical endothelial cells (HUVECs).    Results  We found that PML and TNF α  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 TNF α -mediated immune and inflammatory responses. Furthermore, our data suggest that PML and TNF α  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 TNF α  signaling.    Conclusions  Together, our study identified PML as an essential regulator of TNF α  signaling by revealing the crosstalk between PML knockdown-mediated effects and TNF α -elicited signaling, thereby providing novel insights into TNF α  signaling in endothelial cells.

bmc genomics

Microarray analysis revealing common and distinct functions of promyelocytic leukemia protein (PML) and tumor necrosis factor alpha (TNFα) signaling in endothelial cells