Expression of the phospholipid scramblase (PLSCR) gene family during the acute phase response.
Phospholipid scramblase 1 (PLSCR1) is a member of PLSCR gene family that has been implicated in multiple cellular processes including movement of phospholipids, gene regulation, immuno-activation, and cell proliferation/apoptosis. In the present study, we identified PLSCR1 as a positive intracellular acute phase protein that is upregulated by LPS in liver, heart, and adipose tissue, but not skeletal muscle. LPS administration resulted in a marked increase in PLSCR1 mRNA and protein levels in the liver. This stimulation occurred rapidly (within 2 h), and was very sensitive to LPS (half-maximal response at 0.1 microg/mouse). Moreover, two other APR-inducers, zymosan and turpentine, also produced significant increases in PLSCR1 mRNA and protein levels, indicating that PLSCR1 was stimulated in a number of models of the APR. To determine signaling pathways by which LPS stimulated PLSCR1, we examined the effect of proinflammatory cytokines in vitro and in vivo. TNFalpha, IL-1beta, and IL-6 all stimulated PLSCR1 in cultured Hep B3 hepatocytes, whereas only TNFalpha stimulated PLSCR1 in cultured 3T3-L1 adipocytes, suggesting cell type-specific effects of cytokines. Furthermore, the LPS-stimulated increase in liver PLSCR1 mRNA was greatly attenuated by 80% in TNFalpha and IL-1beta receptor null mice as compared to wild-type controls. In contrast, PLSCR1 levels in adipose tissue were induced to a similar extent in TNFalpha and IL-1beta receptor null mice and controls. These results indicate that maximal stimulation of PLSCR1 by LPS in liver required TNFalpha and/or IL-1beta, whereas the stimulation of PLSCR1 in adipose tissue is not dependent on TNFalpha and/or IL-1beta. These data provide evidence that PLSCR1 is a positive intracellular acute phase protein with a tissue-specific mechanism for up-regulation.
Lu
Biao
B
Metabolism Section, Department of Veterans Affairs Medical Center, University of California San Francisco, 4150 Clement Street, San Francisco, CA 94121, USA. lubiao@gmail.com
Sims
Peter J
PJ
Wiedmer
Therese
T
Moser
Arthur H
AH
Shigenaga
Judy K
JK
Grunfeld
Carl
C
Feingold
Kenneth R
KR
D041721:3T3-L1 Cells; D000210:Acute-Phase Reaction; D000273:Adipose Tissue / Q000201:enzymology; D000818:Animals; D004790:Enzyme Induction; D005260:Female; D017781:Genes, Immediate-Early; D006801:Humans; D053583:Interleukin-1beta / Q000378:metabolism; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism; D008070:Lipopolysaccharides / Q000276:immunology; D008099:Liver / Q000201:enzymology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D005810:Multigene Family; D018482:Muscle, Skeletal / Q000201:enzymology; D009206:Myocardium / Q000201:enzymology; D049294:Phospholipid Transfer Proteins / Q000235:genetics / Q000378:metabolism; D012997:Solvents; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D014425:Turpentine / Q000378:metabolism; D015054:Zymosan / Q000276:immunology
D053583:Interleukin-1beta; D007527:Isoenzymes; D008070:Lipopolysaccharides; D049294:Phospholipid Transfer Proteins; C493426:Plscr1 protein, mouse; D012997:Solvents; D014409:Tumor Necrosis Factor-alpha; D015054:Zymosan; D014425:Turpentine