Lipopolysaccharide decreases scavenger receptor mRNA in vivo.
Lipopolysaccharide (LPS) downregulates scavenger receptor (ScR) activity in cultured macrophages through release of tumor necrosis factor-alpha (TNF-alpha). However, LPS administration in vivo stimulates cytokine release from both macrophages and lymphocytes, the combined effects of which could alter ScR expression differently from TNF-alpha in isolation. To investigate whether LPS regulates ScR in vivo, 10 microg/g was injected i.p. into Swiss Webster mice. Administration of LPS produced a profound decrease in hepatic ScR mRNA, with reductions of 74% +/- 8% at 2 h that returned to baseline levels by 6 h. Changes in ScR mRNA abundance coincided with changes in serum concentrations of TNF-alpha, which peaked at 2 h (1320 +/- 309 pg/ml) and returned to preinjection concentrations at 4 h. Serum concentrations of interferon-gamma (IFN-gamma) did not increase until 4 h after injection of LPS. There was no effect on ScR mRNA abundance following LPS administration to LPS-resistant strains of mice, C3H/HeJ and IFN-gamma receptor-/-. The LPS-induced reduction in ScR mRNA in Swiss Webster mice was not sufficiently sustained to affect receptor function, as determined by the kinetics of [(125)I]-acetylated LDL clearance from plasma. Therefore, as observed in cultured cells, LPS administration to mice decreases ScR mRNA despite the release of several cytokines in vivo.
Roselaar
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Department of Medicine, Washington University School of Medicine, St. Louis, MO, USA.
Daugherty
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D000818:Animals; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008214:Lymphocytes / Q000187:drug effects*; D008264:Macrophages / Q000187:drug effects*; D008565:Membrane Proteins; D051379:Mice; D008809:Mice, Inbred C3H; D011971:Receptors, Immunologic / Q000235:genetics*; D018110:Receptors, Lipoprotein; D051116:Receptors, Scavenger; D051122:Scavenger Receptors, Class B
D008070:Lipopolysaccharides; D008565:Membrane Proteins; D011971:Receptors, Immunologic; D018110:Receptors, Lipoprotein; D051116:Receptors, Scavenger; C454739:Scarb1 protein, mouse; D051122:Scavenger Receptors, Class B