In vivo and in vitro inhibition of JE gene expression by glucocorticoids.
Glucocorticoids are potent anti-inflammatory agents which affect cell growth and migration in a wide variety of systems and have profound effects on monocytes, decreasing their circulating number as well as inhibiting their accumulation at sites of inflammation and injury. Although the mechanisms by which glucocorticoids regulate gene induction have been established, the mechanisms by which they inhibit inflammation or cell growth and migration have yet to been determined. JE is one of the most abundant genes induced by platelet-derived growth factor (PDGF) in vitro and is also induced in vivo in response to ischemia or injury. JE encodes a low molecular weight glycoprotein that functions in part as a monocyte chemotactic factor and thus may be important in recruiting monocytes to sites of tissue injury and/or inflammation. We report that glucocorticoids block the induction of JE mRNA by serum or PDGF in cultured vascular smooth muscle cells. The effect of glucocorticoids appears largely due to destabilization of JE mRNA and has specificity for JE, in that other "early" PDGF-inducible genes are not inhibited by glucocorticoids. The effect of glucocorticoids also occurs in vivo: methyl prednisolone blocks the constitutive expression and inhibits the ischemia-induced elevation of JE mRNA levels in rat kidneys. The inhibition of JE mRNA accumulation by glucocorticoids may be related to the anti-inflammatory effects of these agents and defines JE as a member of what may be a group of PDGF-inducible genes that are responsive to corticosteroids.
Department of Medicine, Mount Sinai School of Medicine, New York, New York 10029.
M
M
Poon
J
J
Megyesi
R S
RS
Green
H
H
Zhang
B J
BJ
Rollins
R
R
Safirstein
M B
MB
Taubman
D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects / Q000502:physiology*; D002478:Cells, Cultured; D003609:Dactinomycin / Q000494:pharmacology*; D003907:Dexamethasone / Q000494:pharmacology*; D015870:Gene Expression / Q000187:drug effects; D006023:Glycoproteins / Q000235:genetics*; D007700:Kinetics; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000502:physiology*; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D014158:Transcription, Genetic / Q000187:drug effects*
D006023:Glycoproteins; D010982:Platelet-Derived Growth Factor; D012333:RNA, Messenger; D003609:Dactinomycin; D003907:Dexamethasone