Lipopolysaccharide inhibits the expression of the scavenger receptor Cla-1 in human monocytes and macrophages.
Human Cla-1 is the likely homologue of the murine scavenger receptor class B type I (SR-BI). SR-BI mediates selective transfer of cholesterol to high-density lipoprotein (HDL) and the efflux of endogenously synthesized and plasma membrane sterols to HDL. HDL protects against atherosclerosis but also reduces endotoxic activity by complexation and neutralization of LPS. We found that Cla-1 is upregulated during phagocytic as well as dendritic differentiation of monocytes, indicating a function of this receptor for cholesterol homeostasis in phagocytes and antigen-presenting cells. Cla-1 expression is suppressed by the proinflammatory stimuli lipopolysaccharide, interferon-gamma, and tumor necrosis factor alpha in monocytes and macrophages. Downregulation of Cla-1 mRNA by LPS is likely due to a modification and subsequent destabilization of the mRNA. We propose that suppression of Cla-1 expression may help to stabilize the lipoprotein status in the blood compartment important for host defense.
Buechler
C
C
Klinikum der Universität Regensburg, Regensburg, D-93042, Germany.
Ritter
M
M
Quoc
C D
CD
Agildere
A
A
Schmitz
G
G
D018955:CD36 Antigens / Q000235:genetics*; D002454:Cell Differentiation; D002784:Cholesterol / Q000378:metabolism; D003513:Cycloheximide / Q000494:pharmacology; D016207:Cytokines / Q000494:pharmacology; D003609:Dactinomycin / Q000494:pharmacology; D003713:Dendritic Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects*; D006207:Half-Life; D006801:Humans; D007249:Inflammation; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008074:Lipoproteins / Q000378:metabolism; D008264:Macrophages / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D009000:Monocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011971:Receptors, Immunologic / Q000235:genetics*; D018110:Receptors, Lipoprotein / Q000235:genetics*; D051116:Receptors, Scavenger; D051122:Scavenger Receptors, Class B
D018955:CD36 Antigens; D016207:Cytokines; D008070:Lipopolysaccharides; D008074:Lipoproteins; D012333:RNA, Messenger; D011971:Receptors, Immunologic; D018110:Receptors, Lipoprotein; D051116:Receptors, Scavenger; C495124:SCARB1 protein, human; D051122:Scavenger Receptors, Class B; D003609:Dactinomycin; D002784:Cholesterol; D003513:Cycloheximide