AUTHOR=Skaria Tom , Bachli Esther , Schoedon Gabriele 

TITLE=Gene Ontology Analysis for Drug Targets of the Whole Genome Transcriptome of Human Vascular Endothelial Cells in Response to Proinflammatory IL-1

JOURNAL=Frontiers in Pharmacology

VOLUME=Volume 10 - 2019

YEAR=2019

URL=https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2019.00414

DOI=10.3389/fphar.2019.00414

ISSN=1663-9812

ABSTRACT=Modulation of proinflammatory responses induced by IL-1β in human vascular endothelial
cells (VEC) to reduce tissue damage is an emerging therapeutic strategy to prevent loss of
organ function during local or systemic inflammatory diseases. The pathways and signalling
molecules involved in IL-1β-induced vascular endothelial inflammation that could be
potential targets for therapeutic modulation remain still poorly addressed.
Our study applies a genome-wide differential expression approach to identify candidate genes
regulated by IL-1β in primary VEC derived from coronary artery (HCAEC). Genes regulated
2-fold were subjected to GO analysis for potential drug targets. We identified HGF as one of
the genes upregulated by IL-1β in HCAEC. Gene ontology analysis mapped HGF to a highly
significant barrier-injuring and repair pathway, and to an inflammatory disease biomarker
network enriched in IL-1β transcriptome in VEC. Further, IL-1β upregulated the expression
of BDKRB2, CTSS, and SERT which are also critically involved in regulating VEC
monolayer barrier function and can be targeted by therapeutic drugs. To our knowledge, the
expression of CTSS and HGF was not yet reported being regulated by IL-1β in human
immunocompetent VEC.
These findings stimulate further studies to evaluate the critical roles and benefits of
therapeutic targeting of BDKRB2, CTSS, HGF, and SERT with known inhibitors to
modulate VEC barrier function, and in consequence, vascular leakage in IL-1β-driven
inflammatory diseases.