Interferon-gamma, tumor necrosis factor-alpha, and lipopolysaccharide promote chitotriosidase gene expression in human macrophages

Human chitotriosidase (Chit), a chitinolytic enzyme, is a member of the chitinase family. In human plasma, Chit activity has been proposed as a biochemical marker of macrophage activation in several lysosomal diseases. Recently we found that Chit activity is higher in patients affected by Plasmodium falciparum malaria infection, suggesting that Chit may reflect induction of an immunological response. To assess this hypothesis, we evaluated the CHIT1 mRNA levels in human monocytes/macrophages (HMMs) following treatment with interferon-gamma (IFN gamma), tumor necrosis factor-alpha (TNF alpha), and lipopolysaccharide (LPS). Stimulation of macrophages with INF-gamma, TNF-alpha, and LPS resulted in an increase in Chit activity as well as the levels of CHIT1 mRNA as measured by quantitative real-time PCR. The data presented in this article show that Chit plays a role in the response to the activation of INF-gamma-, TNF-alpha-, and LPS-driven macrophages, suggesting that the production of Chit by macrophages could have biological relevance in the immune-response. (c) 2005 Wiley-Liss, Inc.