The effect of dexamethasone on the generation of plasma DNA from dead and dying cells.
To determine the effects of glucocorticoids on the clearance of apoptotic and necrotic cells, the influence of dexamethasone on plasma levels of DNA was assessed in BALB/c mice receiving Jurkat cells treated with etoposide or ethanol. In untreated mice, administration of 10(8) apoptotic or necrotic Jurkat cells led to the appearance of DNA in the plasma. In mice treated 24 hours previously with dexamethasone, levels of DNA were reduced in a dose-dependent manner, with mice receiving 1 and 2.5 mg showing no appreciable plasma DNA levels. Similar results were obtained with assay of lactate dehydrogenase in mice receiving apoptotic cells. The effects of dexamethasone on anti-Fas treatment were also characterized. While treatment with a monoclonal anti-Fas reagent caused a significant plasma DNA response in untreated mice, mice pretreated with dexamethasone showed much lower levels. Blood levels of caspase 3 and TUNEL staining of liver were also reduced in dexamethasone-treated mice compared to controls receiving anti-Fas antibody. These results indicate that glucocorticoids can affect the clearance of apoptotic and necrotic cells as well as the induction of apoptosis in at least some tissues. These activities may be relevant to the efficacy of glucocorticoids in the treatment of inflammatory disease.
Jiang
Ning
N
Division of Rheumatology, Duke University Medical Center, Durham, North Carolina, USA.
Pisetsky
David S
DS
D000818:Animals; D018931:Antineoplastic Agents, Hormonal / Q000494:pharmacology; D017209:Apoptosis; D004247:DNA / Q000737:chemistry / Q000187:drug effects*; D003907:Dexamethasone / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D000431:Ethanol / Q000494:pharmacology; D005047:Etoposide / Q000494:pharmacology; D005260:Female; D005434:Flow Cytometry; D005938:Glucocorticoids / Q000378:metabolism; D006801:Humans; D020287:In Situ Nick-End Labeling; D019169:Jurkat Cells; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008099:Liver / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D009336:Necrosis; D013997:Time Factors
D018931:Antineoplastic Agents, Hormonal; D005938:Glucocorticoids; D000431:Ethanol; D005047:Etoposide; D003907:Dexamethasone; D004247:DNA; D007770:L-Lactate Dehydrogenase