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A Proteasome Inhibitor, an Antioxidant, or a Salicylate, but not a
Glucocorticoid, Blocks Constitutive and Cytokine-Inducible Expression
of P-Selectin in Human Endothelial Cells
Lijun Xia,
Junliang Pan,
Longbiao Yao, and
Rodger P. McEver
From the W.K. Warren Medical Research Institute, Departments of
Medicine and Biochemistry and Molecular Biology, University of Oklahoma
Health Sciences Center; and Cardiovascular Biology Research Program,
Oklahoma Medical Research Foundation, Oklahoma City, OK.
Proteasome inhibitors, antioxidants, salicylates, or glucocorticoids
block the cytokine-induced expression of the endothelial cell adhesion
molecules E-selectin, vascular cell adhesion molecule-1, and
intercellular adhesion molecule-1. These pharmacological agents have
been assumed to inhibit the expression of adhesion molecules primarily
by blocking activation of the transcription factor NF- B. We found
that the proteasome inhibitor ALLN, the antioxidant PDTC, or sodium
salicylate, but not the glucocorticoid dexamethasone, inhibited both
the constitutive and the interleukin-4- or oncostatin M-induced
expression of the adhesion molecule P-selectin in human endothelial
cells. ALLN, PDTC, or sodium salicylate decreased P-selectin expression
without a detectable requirement for inhibition of NF-B activation
or for an intact B element in the P-selectin gene. These results
extend the potential anti-inflammatory utility of such drugs to
inhibition of P-selectin expression and suggest that they have
important actions that do not involve the NF-B system.
Blood, Vol. 91 No. 5 (March 1), 1998:
pp. 1625-1632
© 1998 by The American Society of Hematology.
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