Monocytes play a pivotal role in various human infectious and inflammatory diseases. To reveal a whole picture of pathophysiologic function of activated human monocytes, this study used the serial analysis of gene expression (SAGE) procedure in lipopolysaccharide (LPS)-stimulated human monocytes. A total of 35 874 tags corresponding to more than 12 000 different transcripts were sequenced. Comparison of gene expression profile with that of resting monocytes revealed the LPS-inducible gene expression profile. Many cytokines and chemokines, including interleukin (IL)-6, IL-1α, IL-1β, tumor necrosis factor (TNF)-α, macrophage inflammatory protein (MIP)-1β, MIP-2β, MIP-2α, liver and activation-regulated chemokine (LARC), MIP-1α, thymus and activation-regulated chemokine (TARC), macrophage-derived chemokine (MDC), regulated on activation, normal T cell expressed and secreted (RANTES), growth-regulated oncogene (GRO) α, and IL-8, were observed in the highest inducible transcripts. Other genes encoding plasminogen activator inhibitor type 2 (PAI-2), Hc-gp39, apolipoproteins, malate dehydrogenase, matrix metalloproteinase-9 (MMP-9), and cyclooxygenase (COX2) were also highly elevated in LPS-stimulated monocytes. Moreover, up-regulation of Naf1β, IL-7 receptor, adenosine receptor A2a, and many novel genes was newly identified. These results suggest that the LPS-inducible gene products may be involved in cell activation and migration, angiogenesis, tissue remodeling, and metabolism, and thus may orchestrate the inflammatory reactions. On the other hand, the expression of numerous sets of novel genes was discovered to be down-regulated on LPS stimulation. This study represents the first comprehensive analysis of LPS-inducible gene expression 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.

Dendritic cells (DCs) are professional antigen-presenting cells in the immune system and can be generated in vitro from hematopoietic progenitor cells, DC precursors, and monocytes in peripheral blood. Serial analysis of gene expression (SAGE) was conducted in lipopolysaccharide (LPS)-stimulated mature and activated DCs (MADCs) derived from human blood monocytes. A total of 31 837 tag sequences from an MADC cDNA library represented 10 962 different genes, and these data were compared with SAGE data for monocyte-derived immature DCs (IMDCs). Many of the genes, such as germinal center kinase–related protein kinase, cystatin F, interferon (IFN)-α–inducible protein p27, EBI3, HEM45, actin-bundling protein, ELC, DC-LAMP, serine/threonine kinase 4, and several genes in expressed sequence tags, were differentially expressed in MADCs, and those encode proteins related to cell structure, antigen-processing enzymes, chemokines, and IFN-inducible proteins. The profile of MADCs was also compared with that of LPS-stimulated monocytes. The Epstein-Barr virus–induced gene 3 and IFN-α–inducible protein p27 are newly identified to be specifically and highly expressed in MADCs, but not in LPS-stimulated monocytes. The comprehensive identification of specific genes expressed in human IMDCs and MADCs should provide candidate genes to define heterogeneous subsets as well as the function and maturation stage of DCs.

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In response to antigen stimulation, T(h) cells differentiate into two types of effector cells, T(h)1 and T(h)2. T(h)1 cells predominantly mediate cellular immunity, whereas T(h)2 cells induce humoral allergic responses. We have conducted here serial analysis of gene expression (SAGE) in human activated T(h)1- and T(h)2-polarized cells from cord blood. SAGE analysis of 64,510 tags (32,219 and 32,291 tags from T(h)1 and T(h)2 cells respectively) allowed identification of 22,096 different transcripts. In activated T(h)1 cells, many of the known genes (12 genes, P: < 0.01; 56 genes, P: < 0.05), including genes encoding IFN-gamma, lymphotactin, osteopontin, MIP-1alpha, MIP-1beta, perforin, beta-catenin and CD55, are highly expressed. On the other hand, in activated T(h)2 cells rather limited numbers of known genes (four genes, P: < 0.01; 10 genes; P: < 0.05), such as genes encoding FUS, ILF-2, IL-13 and E2-EPF, are found to be selectively expressed. The comprehensive identification of genes selectively expressed in human activated T(h)1 or T(h)2 cells should contribute to our understanding of the molecular basis of T(h)1/T(h)2-dominated human diseases and may provide genetic information to diagnose these diseases.

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