Inverse regulation of the ADAM-family members, decysin and MADDAM/ADAM19 during monocyte differentiation.

Two members of the ADAM (a disintegrin and metalloprotease)-family, MADDAM and decysin, were described as dendritic cell (DC) maturation markers. We are interested in monocyte differentiation and investigated in particular the expression pattern of both genes during the differentiation of human monocytes into DC and macrophages (MAC). Both genes are weakly expressed in freshly isolated monocytes.

Identification of genes expressed in tumor-associated macrophages.

Most malignant tumors contain so-called tumor-associated macrophages (TAM) as a major component of their leukocytic infiltrate. To investigate the impact of the tumor microenvironment on activation and differentiation of macrophages, we established a 3-dimensional model system by culturing human monocytes within multicellular tumor spheroids. After 7 days, monocyte-derived TAM were isolated and analyzed for phenotypic alterations as compared to macrophages cultured without tumor cell contact.

Regulation of 25-hydroxyvitamin D3-1 alpha-hydroxylase and production of 1 alpha,25-dihydroxyvitamin D3 by human dendritic cells.

25-Hydroxyvitamin D3-1 alpha-hydroxylase (25(OH)D3-1 alpha-hydroxylase), the key enzyme of 1 alpha,25-dihydroxyvitamin D3 (1,25(OH)2D3) production, is expressed in monocyte-derived macrophages (MACs). Here we show for the first time constitutive expression of 25(OH)D3-1 alpha-hydroxylase in monocyte-derived dendritic cells (DCs), which was increased after stimulation with lipopolysaccharide (LPS). Accordingly, DCs showed low constitutive production of 1,25(OH)2D3, but activation by LPS increased 1,25(OH)2D3 synthesis.