Rapid nongenomic inhibitory effects of glucocorticoids on phagocytosis and superoxide anion production by macrophages.
Traditionally, steroid hormone effects have been described as a result of the modulation of nuclear transcription, thus triggering genomic events that are responsible for physiological effects. Despite early observations of rapid steroid effects that were incompatible with this theory, nongenomic steroid effects have been widely recognized only recently. However, the nongenomic effect of glucocorticoid (GC) on anti-inflammation and immunosuppression has not been reported. Macrophages play important roles in inflammation and the immune response. The present experiment selected macrophages as experimental cells to explore the nongenomic effects and possible mechanisms of GCs on phagocytosis and superoxide anion production. Phagocytosis by macrophages was detected by the neutral red uptake assay. The superoxide anions were measured by cytochrome C reduction assay. It was found that both 10(-4) and 10(-5) mol/L corticosterone (CORT) rapidly inhibited uptake of neutral red by macrophages in less than 30 min, and the inhibition by the former was stronger than that of the latter. CORT (10(-4) to 10(-10) mol/L) rapidly inhibited superoxide anion production by macrophages in less than 30 min. The above-mentioned effects were insensitive to the GC-receptor antagonist mifepristone (RU486) and the translation inhibitor actidione. CORT coupled to bovine serum albumin (BSA-CORT) was able to mimic the rapid inhibitory effects of CORT. The results indicated that CORT could rapidly inhibit phagocytosis and superoxide anion production by mouse peritoneal macrophages in vitro in less than 30 min by a rapid, nongenomic mechanism, which contributes to the anti-inflammatory and immunosuppressive actions of GCs. These data shed a new light on the clinical application of GCs.
Long
Fei
F
Department of Nautical Medicine, Second Military Medical University, 800 Xiangyin Road, Shanghai 200433, PR China.
Wang
Yun-Xia
YX
Liu
Lei
L
Zhou
Jian
J
Cui
Rui-Yao
RY
Jiang
Chun-Lei
CL
D000818:Animals; D003345:Corticosterone / Q000494:pharmacology*; D008264:Macrophages / Q000187:drug effects* / Q000378:metabolism; D051379:Mice; D008813:Mice, Inbred ICR; D015735:Mifepristone / Q000494:pharmacology; D010587:Phagocytosis / Q000187:drug effects*; D013481:Superoxides / Q000378:metabolism*
D013481:Superoxides; D015735:Mifepristone; D003345:Corticosterone