Glucocorticoids induce differentiation of a specifically activated, anti-inflammatory subtype of human monocytes.
Monocytes and macrophages may either promote or down-regulate inflammatory reactions depending on their state of activation. The effects of glucocorticoids (GCs), the most widely used immunosuppressive drugs, on monocytes are currently not well defined. By analyzing the GC-induced expression pattern in human monocytes by microarray technology, we identified for the first time GC-dependent regulation of 133 genes, including anti-inflammatory molecules such as adenosine A3 receptor, CD1d, and IL-1 receptor II. The results were independently confirmed by real-time polymerase chain reaction (PCR) and flow cytometry. Functional clustering of GC-regulated genes indicated induction of monocytic properties such as phagocytosis and motility as well as repression of adhesion, apoptosis, and oxidative burst. These predictions were confirmed by independent functional assays. GCs up-regulate fMLP receptors and specifically promote chemotaxis to this chemoattractant. Furthermore, GCs promote survival of an anti-inflammatory monocytic phenotype in inflammatory reactions, probably by inhibition of apoptosis because of oxidative stress. GCs limit tissue damage because of induction of antioxidative properties and high capacity for phagocytosis of proinflammatory agents. Thus, GC treatment did not cause a global suppression of monocytic effector functions but results in differentiation of a specific anti-inflammatory phenotype which seems to be actively involved in resolution of inflammatory reactions.
Ehrchen
Jan
J
Institute of Experimental Dermatology, University of Muenster, Germany.
Steinmüller
Lars
L
Barczyk
Katarzyna
K
Tenbrock
Klaus
K
Nacken
Wolfgang
W
Eisenacher
Martin
M
Nordhues
Ursula
U
Sorg
Clemens
C
Sunderkötter
Cord
C
Roth
Johannes
J
D017209:Apoptosis / Q000235:genetics; D002448:Cell Adhesion / Q000235:genetics; D002454:Cell Differentiation / Q000187:drug effects*; D002465:Cell Movement / Q000235:genetics; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000187:drug effects*; D005938:Glucocorticoids / Q000494:pharmacology*; D006801:Humans; D007249:Inflammation / Q000235:genetics*; D009000:Monocytes / Q000187:drug effects*; D010587:Phagocytosis / Q000235:genetics; D010641:Phenotype; D016897:Respiratory Burst / Q000235:genetics
D005938:Glucocorticoids