Glucocorticoids negatively regulate the transcription of KC, the mouse homolog of MGSA/GRO.
The KC gene is a member of the small inducible gene family of regulated chemokines. It encodes a growth factor and chemoattractant that appears to mediate inflammatory and immune responses in vitro and in vivo. We now show that the transcriptional induction of KC by serum is inhibited by glucocorticoids. The effect of glucocorticoids is dose-dependent, requires one hour of exposure, is reversed by the protein synthesis inhibitors puromycin and cycloheximide and acts at the transcriptional level. The results support the hypothesis that the major anti-inflammatory action of glucocorticoids may be to inhibit the induction of immediate-early genes that encode cytokines involved in intercellular communication.
Deng
Z W
ZW
Department of Medicine, Washington University, St. Louis, Missouri 63110.
Denkinger
D J
DJ
Peterson
K E
KE
Deuel
T F
TF
Kawahara
R S
RS
D016475:3T3 Cells; D000818:Animals; D015152:Blotting, Northern; D054360:Chemokine CXCL1; D018925:Chemokines; D019743:Chemokines, CXC; D002630:Chemotactic Factors / Q000096:biosynthesis*; D003513:Cycloheximide / Q000494:pharmacology; D016207:Cytokines / Q000096:biosynthesis*; D003907:Dexamethasone / Q000494:pharmacology*; D005786:Gene Expression Regulation / Q000187:drug effects*; D005938:Glucocorticoids / Q000494:pharmacology*; D006133:Growth Substances / Q000096:biosynthesis*; D036341:Intercellular Signaling Peptides and Proteins; D051379:Mice; D008807:Mice, Inbred BALB C; D005810:Multigene Family; D011691:Puromycin / Q000494:pharmacology; D012333:RNA, Messenger / Q000096:biosynthesis; D014158:Transcription, Genetic / Q000187:drug effects*
D054360:Chemokine CXCL1; D018925:Chemokines; D019743:Chemokines, CXC; D002630:Chemotactic Factors; C475895:Cxcl1 protein, mouse; D016207:Cytokines; D005938:Glucocorticoids; D006133:Growth Substances; D036341:Intercellular Signaling Peptides and Proteins; D012333:RNA, Messenger; C074302:keratinocyte-derived chemokines; D011691:Puromycin; D003907:Dexamethasone; D003513:Cycloheximide