The Scavenger Receptor CD163: Regulation, Promoter Structure and Genomic Organization

Abstract

CD163 is a recently identified member of the scavenger receptor cysteine-rich superfamily expressed on peripheral blood monocytes and most tissue macrophages. We demonstrate that in vitro culture of human blood monocytes with recombinant M-CSF induces CD163 transcription. In contrast, dendritic differentiation in the presence of GM-CSF and IL-4 suppresses CD163 mRNA and protein levels. Because an important function of CD163 in inflammation has been suggested, we investigated the influence of pro- and anti-inflammatory stimuli on CD163 expression and found a significant suppression by lipoposaccharide and IFN-γ, whereas IL-10 or dexamethasone strongly induced the expression of CD163. The induction of CD163 mRNA by dexamethasone is suggested to be mediated by several glucocorticoid receptor binding sites located in the proximal promoter region. In addition, this sequence contains potential binding sites for the transcription factors Sp1, C/EBPα, Ets-2, PU.1 and AP-1, which have been shown to play an important role in myeloid-specific gene expression. We also identified an L1-transposable element 1.4 kb upstream of the transcription start site that might influence the promoter activity. The function of CD163 may also depend on the use of different isoforms. Several variants of CD163 mRNA have been described that encode proteins with altered cytoplasmic or extracellular domains and thus may differ in their functional properties. We analyzed the genomic organization of the CD163 gene and could demonstrate that these isoforms result from alternative splicing. Further characterization of the isoforms may help to understand the complete function of CD163.