Dexamethasone suppression of IL-1 beta-induced cyclooxygenase 2 expression is not mediated by lipocortin-1 in A549 cells.
A549 cells grown under serum free conditions do not express cyclooxygenase 2 (cox 2). However, addition of IL-1 beta results in the induction of cox 2 in a time and dose dependent manner; actinomycin D completely blocks this induction. Dexamethasone completely suppressed the induction of cox 2 only if present during the first 3.5h of IL-1 beta treatment but not if added after 3.5h. Treatment with a neutralising monoclonal antibody (1A, Biogen) specific to lipocortin-1 failed to reverse this inhibition by dexamethasone. However, using this same antibody we were able to reverse completely the effects of dexamethasone on the suppression of PGE2 release. These observations support the idea that glucocorticoids directly regulate cox 2 expression at the transcriptional level and this phenomenon is not mediated by lipocortin-1.
Newman
S P
SP
Department of Biochemical Pharmacology, William Harvey Research Institute, Medical School of St. Batholomew's Hospital, London, UK.
Flower
R J
RJ
Croxtall
J D
JD
D017302:Annexins / Q000276:immunology / Q000502:physiology; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D002460:Cell Line; D003513:Cycloheximide / Q000494:pharmacology; D003609:Dactinomycin / Q000494:pharmacology; D003907:Dexamethasone / Q000494:pharmacology*; D015232:Dinoprostone / Q000378:metabolism; D004815:Epidermal Growth Factor / Q000494:pharmacology; D015870:Gene Expression / Q000187:drug effects*; D007375:Interleukin-1 / Q000494:pharmacology*; D011451:Prostaglandin-Endoperoxide Synthases / Q000096:biosynthesis / Q000235:genetics*
D017302:Annexins; D000911:Antibodies, Monoclonal; D007375:Interleukin-1; D003609:Dactinomycin; D004815:Epidermal Growth Factor; D003907:Dexamethasone; D003513:Cycloheximide; D011451:Prostaglandin-Endoperoxide Synthases; D015232:Dinoprostone