title: Impaired IL-10 transcription and release in animal models of Gaucher disease macrophages.
abstract: 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 TNFalpha 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.
authors.affiliation: Department of Biological Chemistry, Weizmann Institute of Science, Rehovot, Israel.
authors.forename: Yaacov
authors.initials: Y
authors.lastname: Kacher
authors.forename: Anthony H
authors.initials: AH
authors.lastname: Futerman
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D005776:Gaucher Disease / Q000139:chemically induced / Q000235:genetics / Q000276:immunology*; D005962:Glucosylceramidase / Q000037:antagonists & inhibitors; D007294:Inositol / Q000031:analogs & derivatives; D016753:Interleukin-10 / Q000235:genetics* / Q000276:immunology*; D008264:Macrophages / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D012333:RNA, Messenger / Q000235:genetics; D014158:Transcription, Genetic; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology
chemical_list: D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D007294:Inositol; D005962:Glucosylceramidase; C011423:conduritol epoxide