Effect of interferon-gamma, interleukin-10, lipopolysaccharide and tumor necrosis factor-alpha on chitotriosidase synthesis in human macrophages

Human chitotriosidase is a chitinolytic enzyme and mainly produced by activated macrophages. Recently, we observed that prolactin, which is structurally related to several cytokines and is involved in regulating monocyte/macrophage functions, upregulates chitotriosidase gene expression in human macrophages, suggesting that chitotriosidase is not only a biochemical marker of macrophage activation in lysosomal diseases and hematological disorders, but also may reflect induction of an immunological response. To confirm this hypothesis we evaluated by quantitative real-time PCR the mRNA chitotriosidase levels in human monocytes/macrophages following treatment with pro-inflammatory stimuli such as interferon-gamma, tumor necrosis factor-alpha, lipopolysaccharide, and interleukin-10, an anti-inflammatory cytokine. Stimulation of macrophages with interferon-gamma, tumor necrosis factor-alpha and lipopolysaccharide resulted in increased levels of chitotriosidase mRNA, as well as chitotriosidase activity, whereas interleukin-10 decreased chitotriosidase synthesis. This finding is consistent with the hypothesis that the production of chitotriosidase by macrophages could have biological relevance in the immune response.