Effects of glucocorticoids on apoptosis of infiltrated eosinophils and neutrophils in rats.
The effects of glucocorticoids on the survival of rat eosinophils and neutrophils infiltrated into the peritoneal cavity were examined. Glucocorticoids including dexamethasone, prednisolone and hydrocortisone inhibited the survival of rat peritoneal eosinophils at 10(-6) M, whereas they prolonged survival of rat peritoneal neutrophils at 10(-8) M. Sex steroids including estradiol and progesterone did not affect cell survival. Dexamethasone decreased the viability of eosinophils after 3 days of incubation and maintained the viability of neutrophils until 4 days after incubation concentration dependently. The EC50 of dexamethasone for inhibition of the survival of eosinophils was 1.5 x 10(-8) M, and that for the spontaneous death of neutrophils was 6.4 x 10(-10) M, suggesting that glucocorticoids at concentrations that inhibit eosinophil survival prolong neutrophil survival. Analysis of DNA fragmentation of cultured eosinophils and neutrophils revealed that glucocorticoids enhance eosinophil apoptosis but inhibit neutrophil apoptosis. The effects of dexamethasone on viability and DNA fragmentation were counteracted by the glucocorticoid receptor antagonist, mifepristone, concentration dependently. These findings indicate that glucocorticoids induce contradictory effects via the glucocorticoid receptor on rat eosinophils and neutrophils extravasated to an inflammatory locus such as the peritoneal cavity by modulating apoptosis.
Nittoh
T
T
Department of Pathophysiological Biochemistry, Faculty of Pharmaceutical Sciences, Tohoku University, Sendai, Miyagi, Japan.
Fujimori
H
H
Kozumi
Y
Y
Ishihara
K
K
Mue
S
S
Ohuchi
K
K
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D004247:DNA / Q000187:drug effects / Q000378:metabolism; D004249:DNA Damage; D003907:Dexamethasone / Q000494:pharmacology; D004804:Eosinophils / Q000166:cytology* / Q000187:drug effects*; D005938:Glucocorticoids / Q000502:physiology*; D006854:Hydrocortisone / Q000494:pharmacology; D008297:Male; D015735:Mifepristone / Q000494:pharmacology; D009504:Neutrophils / Q000166:cytology* / Q000187:drug effects*; D010529:Peritoneal Cavity / Q000166:cytology; D011239:Prednisolone / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley
D000893:Anti-Inflammatory Agents; D005938:Glucocorticoids; D015735:Mifepristone; D003907:Dexamethasone; D004247:DNA; D011239:Prednisolone; D006854:Hydrocortisone