Divergent inducible expression of P-selectin and E-selectin in mice and primates.
We used in vitro and in vivo approaches to examine whether tumor necrosis factor-alpha (TNF-alpha) and oncostatin M (OSM), cytokines that bind to distinct classes of receptors, differentially regulate expression of P- and E-selectin in murine and primate endothelial cells. In human umbilical vein endothelial cells, TNF-alpha rapidly increased mRNA for E-selectin but not P-selectin. OSM elicited little or no change in mRNA for E-selectin, but induced a delayed and prolonged increase in P-selectin mRNA. TNF-alpha and OSM did not cooperate to further enhance P- or E-selectin mRNA. Intravenous infusion of Escherichia coli, which markedly elevates plasma lipopolysaccharide and TNF-alpha, increased mRNA for E-selectin but not P-selectin in baboons. In murine bEnd.3 endothelioma cells, TNF-alpha and OSM individually and cooperatively increased mRNA and protein for both P- and E-selectin. Intravenous injection of these cytokines also individually and cooperatively increased mRNA for P- and E-selectin in mice. We conclude that the murine P- and E-selectin genes respond to both TNF-alpha and OSM, whereas the primate P- and E-selectin genes have much more specialized responses. Such differences should be considered when extrapolating the functions of P- and E-selectin in murine models of inflammation to humans.
Yao
L
L
W.K. Warren Medical Research Institute, Department of Medicine, University of Oklahoma Health Sciences Center, Oklahoma City 73104, USA.
Setiadi
H
H
Xia
L
L
Laszik
Z
Z
Taylor
F B
FB
McEver
R P
RP
D000818:Animals; D019040:E-Selectin / Q000096:biosynthesis / Q000235:genetics*; D005786:Gene Expression Regulation / Q000187:drug effects*; D006801:Humans; D051379:Mice; D053683:Oncostatin M; D019007:P-Selectin / Q000096:biosynthesis / Q000235:genetics*; D010455:Peptides / Q000494:pharmacology*; D011323:Primates; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D013045:Species Specificity; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
D019040:E-Selectin; C508351:OSM protein, human; C508352:Osm protein, mouse; D019007:P-Selectin; D010455:Peptides; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D053683:Oncostatin M