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

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