Heme oxygenase-1 transduction in endothelial cells causes downregulation of monocyte chemoattractant protein-1 and of genes involved in inflammation and growth.
Heme oxygenase (HO-1) has been implicated as an anti-inflammatory gene. HO-1 overexpression, transiently and chronically, affects heme protein expression, attenuates TNF-mediated cell death, and decreases adhesion molecules. We assessed the effect of oxidant-mediated agents such as glucose and heme on 8-epi-isoprostane PGF2alpha (8-epi-PGF2alpha) and monocyte chemoattractant protein-1 (MCP-1). Glucose and heme increased both 8-epi-PGF2alpha and MCP-1. Overexpression of HO-1 decreased both 8-epi-PGF2alpha and MCP-1. To identify target genes involved in HO-1-mediated regulation of inflammation, a serial analysis of gene expression mRNA profile was performed in endothelial cells (EC) overexpressing the human HO-1 gene by transduction of a retrovirus carrying the HO-1 gene. Gene arrays (differential displays among 2400 genes) were used to identify known and novel differentially expressed genes. The levels of expression for several genes were confirmed by real time PCR in cells overexpressing the HO-1 gene. In HO-1 overexpressing cells, VEGF and the prostaglandin transporter were greatly increased while MCP-1 levels were decreased by 2.5-fold. The data from this study are relevant to understanding the mechanisms underlying the pathophysiological effects of HO-1 deficiency on endothelial cell injury and inflammation.
Sacerdoti
D
D
Department of Clinical and Experimental Medicine, Clinica Medica 5, University of Padova, Via Giustiniani 2, 35100 Padova, Italy. david.sacerdoti@unipd.it
Colombrita
C
C
Ghattas
M H
MH
Ismaeil
E F
EF
Scapagnini
G
G
Bolognesi
M
M
Li Volti
G
G
Abraham
N G
NG
D002453:Cell Cycle / Q000235:genetics*; D002478:Cells, Cultured; D018932:Chemokine CCL2 / Q000378:metabolism*; D015536:Down-Regulation; D042783:Endothelial Cells / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D015971:Gene Expression Regulation, Enzymologic; D005947:Glucose / Q000494:pharmacology; D006418:Heme / Q000494:pharmacology; D051547:Heme Oxygenase-1 / Q000235:genetics* / Q000378:metabolism*; D006801:Humans; D007249:Inflammation / Q000235:genetics; D015854:Up-Regulation / Q000235:genetics
D018932:Chemokine CCL2; D006418:Heme; D051547:Heme Oxygenase-1; D005947:Glucose