ASGSB 2007 Abstracts - Activation and Regulation of Monocyte Differentiation

ASGSB 2007 Annual Meeting Abstracts

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Activation and Regulation of Monocyte Differentiation C-F. Li and M. Hughes-Fulford, Lab of Cell Growth, UCSF, NCIRE, and VAMC, San Francisco, CA.

Early space flight experiments have shown that microgravity suppresses the immune response in humans. Space shuttle experiments have shown that there is a significant decrease in differentiation of monocytes into macrophages in returning astronauts. Protein Kinase C (PKC) is a key protein in the differentiation of monocytes into macrophages. Phorbol esters are used in the laboratory to stimulate differentiation. We have found that simulated microgravity can inhibit differentiation of monocytes. We have conducted studies of PKC differentiation using phorbol 12,13-dibutyrate (PDBu) using microarray analysis to identify key genes regulating human U937 monocyte differentiation. Activation causes dramatic and significant induction of gene expression with the highest increase at 3 hours with a 31 fold and at 36 hours the highest increase was 2,100 fold. We found that after 3 hours of treatment, over 700 genes significantly increased and at 36 hours over 4,000 genes were significantly induced by at least 2-fold over controls. Gene Ontology analysis demonstrated that there is significant increases in chemokines, receptors, differentiation, GTPase, cytoskeletal and adhesion genes over the 36 hour period. This data will be used to analyze samples from our ISS experiments to discover which genes require gravity for normal gene induction. (Supported by NASA NCC 2-1361)