Promoter-mediated, dexamethasone-induced increase in cystatin C production by HeLa cells.
Cystatin C, an efficient inhibitor of cysteine proteinases, is present in all investigated human extracellular fluids. Dexamethasone caused a significant and dose-dependent increase in the cystatin C secretion of cultivated HeLa cells up to a maximal increase of 80% at 10(-6) mol l-1 dexamethasone. Increased production of cystatin C was also observed at lower concentrations, suggesting that glucocorticoids might play a physiological role in the production of cystatin C. The effect of dexamethasone on the cystatin C gene expression was also studied in a transient transfection expression system using chimeric plasmid constructs of the cystatin C gene promoter (positions -2 to -1084) coupled to the structural gene for human growth hormone (hGH). In this system, a small, but statistically significant, increase in hGH secretion was also observed upon dexamethasone treatment, suggesting that the glucocorticoid-induced increase in secretion of cystatin C is due to a promoter-mediated increase in transcription of the cystatin C gene.
Bjarnadóttir
M
M
Department of Clinical Chemistry, University Hospital, Lund, Sweden.
Grubb
A
A
Olafsson
I
I
D055316:Cystatin C; D015891:Cystatins / Q000235:genetics / Q000378:metabolism*; D015853:Cysteine Proteinase Inhibitors / Q000235:genetics / Q000378:metabolism*; D003907:Dexamethasone / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005786:Gene Expression Regulation / Q000187:drug effects; D005938:Glucocorticoids / Q000494:pharmacology*; D013006:Growth Hormone / Q000096:biosynthesis / Q000187:drug effects; D006367:HeLa Cells / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D011401:Promoter Regions, Genetic / Q000187:drug effects*; D013997:Time Factors; D014158:Transcription, Genetic / Q000235:genetics; D014162:Transfection
C525030:CST3 protein, human; D055316:Cystatin C; D015891:Cystatins; D015853:Cysteine Proteinase Inhibitors; D005938:Glucocorticoids; D003907:Dexamethasone; D013006:Growth Hormone