Effects of dexamethasone on rat dendritic cell function.
Glucocorticoids have been reported to affect immunity at varying concentrations. While glucocorticoids have shown profound effects on innate immunity, their effects on rat dendritic cells have not been fully examined. In this study, we evaluated the effects of the synthetic glucocorticoid dexamethasone on cultured rat dendritic cells (DCs) from spleen and derived from bone marrow cells to determine whether responsiveness to dexamethasone varies between DCs from different organ sites. Cells were analyzed for expression of glucocorticoid receptor (GR), the primary receptor through which dexamethasone exerts its effects and was found to be primarily located in the cytoplasm of immature DCs. Bone marrow-derived DCs showed more sensitivity to dexamethasone treatment compared to splenic DCs. Dexamethasone treatment of LPS-matured DCs had profound dose-dependent effects on cytokine production. Dexamethasone treatment also led to a dose-dependent downregulation of expression of costimulatory molecules by mature DCs. Dexamethasone modified immature DC uptake of antigen (FITC-Dextran), with slightly higher numbers of splenic DCs taking up antigen compared to bone marrow-derived DCs. These data suggest that dexamethasone is able to similarly affect both bone marrow-derived and splenic DC function at the immature and mature DC states and could contribute to exacerbation of infection by hindering DC-mediated immune responses.
Butts
C L
CL
Section on Neuroendocrine Immunology & Behavior, National Institute of Mental Health/NIH, Bethesda, MD 20892, USA.
Shukair
S A
SA
Duncan
K M
KM
Harris
C W
CW
Belyavskaya
E
E
Sternberg
E M
EM
D000818:Animals; D001854:Bone Marrow Cells / Q000187:drug effects / Q000502:physiology; D016207:Cytokines / Q000096:biosynthesis; D003713:Dendritic Cells / Q000187:drug effects* / Q000502:physiology; D003907:Dexamethasone / Q000494:pharmacology*; D005260:Female; D008070:Lipopolysaccharides / Q000494:pharmacology; D051381:Rats; D011916:Rats, Inbred F344; D013154:Spleen / Q000166:cytology
D016207:Cytokines; D008070:Lipopolysaccharides; D003907:Dexamethasone