Septicemia and Shock: Pathogenesis and Novel Therapeutic Strategies
(2003, NS 124)
Anna Norrby-Teglund, Staffan Normark, Ragnar Norrby, Malak Kotb, Thierry Calandra, Terje Espevik
May 15 - 17
Nobel Forum, Karolinska Institutet, Stockholm, Sweden
Proceedings: Scandinavian Journal of Infectious Diseases, Vol. 35, No. 9, 2003, Stockholm.

 

LPS-inducible Gene Expression Profile in Human Monocytes
Shin-ichi Hashimoto, Kei Morohoshi, Takuji Suzuki and Kouji Matsushima
Department of Molecular Preventive Medicine, School of Medicine, The University of Tokyo, Tokyo, Japan

Monocytes/macrophages play a key role in host defense by phagocytosing invaded pathogens, presenting antigens to immune cells, and producing numerous inflammatory mediators. Although the expression of many proteins and genes have been described to be upregulated in activated human monocytes, a whole picture of pathophysiologic function of activated human monocytes has not yet been drawn. We have applied here the serial analysis of gene expression (SAGE) procedure to lipopolysaccharide (LPS)-stimulated human monocytes. A total of 35,874 tags corresponding to more than 12,000 different transcripts were sequenced. In addition, the Long SAGE was conducted in LPS-stimulated monocytes to increase the accuracy of corresponding gene identification. Comparison of gene expression profile with that of resting monocytes revealed the whole LPS-inducible gene expression profile. The functional classifications of LPS-inducible genes( greater than 8 fold increase compared with resting monocytes) in monocytes showed that 25% of inducible genes were identified to encode cytokines and chemokines, followed by proteins related to metabolism (11%), cell surface antigens (9%), nuclear proteins (8%), proteases (6%), proteins related to extracellular transport (4%) and intracellular transducers (4%). Moreover, 14% of LPS-inducible genes still encode proteins with unknown function.

This study represents the first global analysis of LPS-inducible genes in human monocytes and provides tremendous novel information for the function of LPS-activated monocytes and targets for diagnosing, monitoring, and treating sepsis and various human infectious and inflammatory diseases.