Regulation of CD14 expression on human adult central nervous system-derived microglia

Abstract

Microglial cells function as regulators of immune reactivity within the CNS and may contribute to tissue injury under inflammatory conditions. Such functions are correlated with their state of activation. In this study, we report the de novo expression of CD14 by adult human CNS-derived microglia which acquire a bipolar activated morphologic phenotype in dissociated tissue culture. Surface CD14 expression can be down-regulated by interaction with its ligand lipopolysaccharide (LPS), and by the T-helper (Th1) cytokine interferon-gamma (IFN-gamma) or the Th2 cytokine interleukin-4 (IL-4). Semiquantitative polymerase chain reaction (PCR) analysis of CD14 mRNA expression under each condition suggests a different mechanism accounting for the reduced surface expression. LPS down-regulates CD14 mRNA, consistent with a feed-back signal preventing over-stimulation. IFN-gamma augments CD14 transcription, suggesting cleavage of surface CD14 consequent to general cell activation. IL-4 decreases mRNA production likely reflecting a generalized suppressive effect. The effect of LPS, IFN-gamma and IL-4 on CD14 expression differes from their effect on expression of the immune-accessory molecules B7-1 and HLA-DR, and on production of tumor necrosis factor-alpha (TNF-alpha), whose secretory pathway is similar to that of CD14. These results indicate the selective effects of molecules, likely to be present in the infected or inflamed CNS, on regulating CD14 expression and that there can be differential regulation of immune response relevant molecules expressed by activated microglia.