Chronic Beryllium Disease (CBD) is an occupationally acquired lung disease that occurs as a cell mediated immune response to beryllium, resulting in the development of noncaseating granulomas. We hypothesized that the identification of early genes associated with beryllium exposure may give important insights into the role of macrophages in CBD. We investigated gene expression in a mouse alveolar macrophage cell line incubated in the presence of absence of 10microM BeSO4 for 4 hours. We utilized Affymetrix oligonucleotide arrays consisting of approximately 12000 genes to detect differential changes in gene expression in beryllium-treated cells compared to controls. We found that beryllium caused significant changes in the expression of numerous genes encoding; heat shock proteins, cytokines, adhesion molecules, cytokine receptors, signalling molecules and transcriptional activators and repressors. HSP70 and MHC class III region were elevated 10-fold in BeSO4 treated macrophages. However, IL- 1[beta], ICE, ICAM-1 and IL-10R were all decreased by beryllium. We verified beryllium-modulation of these genes by real time quantification (TaqmanTMPCR). Our studies identify beryllium-regulated genes and suggest that HSPs and cytokine genes play pivotal roles in an early immune response to beryllium.
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