Glucocorticoid-induced reduction of prostanoid synthesis in TPA-differentiated U937 cells is mainly due to a reduced cyclooxygenase activity

Biochemical Pharmacology
L KoehlerM Goppelt-Struebe

Abstract

The molecular mechanism of the glucocorticoid-induced inhibition of prostanoid synthesis was investigated in human monoblastoid U937 tumor cells and phorbol ester (TPA)-differentiated U937 cells. Prostanoid synthesis was inhibited in TPA-differentiated U937 cells by glucocorticoids such as dexamethasone and prednisolone, whereas aldosterone and progesterone showed no inhibitory effect. None of these methods had any influence on prostanoid secretion of undifferentiated U937 cells. Receptor binding studies revealed the presence of glucocorticoid receptors in both undifferentiated and TPA-differentiated U937 cells (Kp approximately 5 x 10(-9)M), however, the number of receptors per cell was increased 10-fold in TPA-differentiated U937 cells. Expression of lipocortin I and II as measured by Western blot analysis was not affected by dexamethasone. In TPA-differentiated cells, dexamethasone decreased the activities of two enzymes essential for prostanoid synthesis, cyclooxygenase and phospholipase A2, by 60-70% and 30%, respectively. Cells pretreated with the translation inhibitor cyclohexmide and dexamethasone showed similar cyclooxygenase and phospholipase A2 activities as cells treated with cycloheximide alone. Western blot analys...Continue Reading

References

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Citations

Dec 1, 1994·Cancer Metastasis Reviews·H R Herschman
Jan 5, 1996·Biochimica Et Biophysica Acta·H R Herschman
Jan 1, 1991·Pharmacology & Therapeutics·W L SmithD L DeWitt
Oct 1, 1993·Neurochemistry International·D B StanimirovicM Spatz
Nov 1, 1995·Trends in Endocrinology and Metabolism : TEM·R P Robertson
Feb 24, 2006·Nature Reviews. Immunology·Christopher K Glass, Sumito Ogawa
Jun 1, 1992·Proceedings of the National Academy of Sciences of the United States of America·M K O'BanionD A Young
Sep 5, 2012·Cell Communication and Signaling : CCS·Ralf Hass, Anna Otte
Feb 1, 1992·Prostaglandins, Leukotrienes, and Essential Fatty Acids·D Duval, M Freyss-Beguin
Dec 31, 2003·Biochemical Pharmacology·Annabel F Valledor, Mercedes Ricote
Feb 28, 2007·British Journal of Cancer·A M E BruynzeelW J F van der Vijgh
Jun 28, 2014·International Journal of Oncology·Anna OtteRalf Hass
Apr 1, 1995·Prostaglandins, Leukotrienes, and Essential Fatty Acids·M Goppelt-Struebe

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