Induction of heme oxygenase-1 inhibits monocyte chemoattractant protein-1 mRNA expression in U937 cells.
Heme oxygenase-1 (HO-1) is a stress-inducible isoform of HO with potential cytoprotective effects. Monocyte activation/migration mediated by monocyte chemoattractant protein-1 (MCP-1) is one of the earliest and important events in the pathogenesis of atherosclerosis. We examined the effect of HO-1 on the production of lysophosphatidylcholine (Lyso-PC)-induced MCP-1 in the human promonocytic cell line U937. Increased HO-1 induction by hemin resulted in a significant decrease in the Lyso-PC-mediated induction of MCP-1 mRNA expression. SnPP (IX), the specific inhibitor of HO-1 enzymatic activity, prevented the hemin-mediated attenuation of MCP-1 mRNA expression. These results suggest that HO-1 may work as an anti-atherogenic agent through the attenuation of MCP-1 production.
Department of Molecular and Internal Medicine, Graduate School of Biomedical Sciences, Hiroshima University, Hiroshima, Japan.
Tomoki
T
Shokawa
Masao
M
Yoshizumi
Hideya
H
Yamamoto
Shinji
S
Omura
Mamoru
M
Toyofuku
Yoshito
Y
Shimizu
Michinori
M
Imazu
Nobuoki
N
Kohno
D018932:Chemokine CCL2 / Q000037:antagonists & inhibitors* / Q000235:genetics; D004305:Dose-Response Relationship, Drug; D004790:Enzyme Induction; D005786:Gene Expression Regulation / Q000187:drug effects*; D051547:Heme Oxygenase-1 / Q000096:biosynthesis* / Q000235:genetics; D006801:Humans; D008244:Lysophosphatidylcholines / Q000494:pharmacology*; D009000:Monocytes / Q000166:cytology / Q000187:drug effects*; D012333:RNA, Messenger / Q000378:metabolism*; D012337:RNA, Ribosomal, 18S / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013997:Time Factors; D020298:U937 Cells
D018932:Chemokine CCL2; D008244:Lysophosphatidylcholines; D012333:RNA, Messenger; D012337:RNA, Ribosomal, 18S; D051547:Heme Oxygenase-1