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

http://www.ncbi.nlm.nih.gov/pubmed/19380242?dopt=Abstract

Kacher Y, Futerman AH.

Department of Biological Chemistry, Weizmann Institute of Science, Rehovot, Israel.

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.

Publication Types:

• Research Support, Non-U.S. Gov’t

PMID: 19380242 [PubMed – in process] Kacher Y, Futerman AH.