Impaired IL-10 transcription and release in animal models of Gaucher disease macrophages

• Published in: Blood cells, molecules, & diseases molecules, & diseases, 2009-07, Vol.43 (1), p.134-137
• Main Authors: Kacher, Yaacov, Futerman, Anthony H.
• Format: Article
• Language: English
• Subjects: Animals; Cells, Cultured; Gaucher disease; Gaucher Disease - chemically induced; Gaucher Disease - genetics; Gaucher Disease - immunology; Glucosylceramidase - antagonists & inhibitors; Inositol - analogs & derivatives; Interleukin-10; Interleukin-10 - genetics; Interleukin-10 - immunology; Macrophages; Macrophages - immunology; Mice; Mice, Inbred C57BL; RNA, Messenger - genetics; TNFα; Transcription, Genetic; Tumor Necrosis Factor-alpha - immunology
• ISSN: 1079-9796; 1096-0961
• DOI: 10.1016/j.bcmd.2009.03.006

A number of studies have shown altered cytokine levels in serum from Gaucher disease patients, including changes in levels of the anti-inflammatory cytokine, interleukin-10 (IL-10). However, the source of IL-10, or the mechanisms leading to changes in IL-10 serum levels are not known. We now show that mouse macrophages treated with an active site-directed inhibitor of glucocerebrosidase, or macrophages from a mouse model of Gaucher disease, the L444P mouse, release significantly less IL-10 than their untreated counterparts, but that TNFα release is unaffected. These changes are due to reduced transcription of IL-10 mRNA in macrophages. The reduction in IL-10 secretion observed in animal models of Gaucher disease macrophages may be of relevance to explain the increase in inflammation that is often observed in Gaucher disease.