The role of zinc in calprotectin expression in human myeloid cells

Elevated levels of calprotectin and other inflammatory mediators have been observed in inflammatory diseases paralleling serum hypozincemia. While a role of zinc in the regulation of tumor necrosis factor α, interleukin (IL)-1β and IL-6 expression has been established, the direct interrelation of zinc and calprotectin (S100A8/S100A9 heterodimer) expression is so far missing. In the present study, we analyzed mRNA and protein levels of S100A8 and S100A9 in monocytic Mono Mac (MM)1 and early myeloid THP-1 and U937 cells to elucidate the effect of zinc deficiency on their expression. We could depict that zinc deficiency alone enhances mRNA and protein expression of calprotectin in myeloid cells, independently from maturity stage. Moreover, pre-existing zinc deficiency augmented lipopolysaccharide (LPS)-induced calprotectin expression in CD14⁺ MM1, but not in CD14^- U937 or CD14^- THP-1 cells. Zinc deficiency and LPS seem therefore to activate different intracellular pathways. Our findings suggest that zinc does not only regulate the activity of calprotectin but also its expression by human myeloid cells.