Early gene changes in a mouse alveolar macrophage cell line in response to beryllium.
Am J Respir Crit Care Med 2003 Apr; 167(7):A340
Chronic Beryllium Disease (CBD) is an occupationally acquired lung disease that occurs as a cell mediated immune response to beryllium particles, 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 macro phages in CBD. We investigated multiple gene expression in a mouse alveolar macrophage (MH-S) cell line incubated in the presence or absence of 10uM BeSO4 for 4 hours. We assessed cell viability following 4 hour incubation with beryllium and we determined that the cells were 95% viable and the proliferation rate matched those of unstimulated controls. 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. Strikingly, heat shock protein and MHC class III region were elevated 10-fold in BeSO4. treated macrophages. We verified that HSP70 mRNA was up-regulated over 10-fold by real time quantification (Taqman TM PCR). The MHC class III region encodes heat shock proteins of the 70kDa family. HSP70 molecules playa critical role in cytoprotection against toxic exposures and are important as molecular chaperones in antigen processing and presentation. Our studies identify beryllium-regulated genes and suggest that HSP70, in particular, may playa pivotal role in cytoprotection and the early immune response to beryllium salts.
Genes; Alveolar-cells; Beryllium-compounds; Lung-disease; Pulmonary-system-disorders; Toxins; Heavy-metals; Heavy-metal-poisoning
Abstract; Conference/Symposia Proceedings
Research Tools and Approaches: Exposure Assessment Methods
American Journal of Respiratory and Critical Care Medicine