Comprehensive gene expression profile of LPS-stimulated human monocytes bySAGE

Monocytes play a pivotal role in various human infectious and inflammatory diseases. To reveal a whole picture of pathophysiologic function of activat ed 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 transcript s were sequenced. Comparison of gene expression profile with that of restin g monocytes revealed the LPS-inducible gene expression profile. Many cytoki nes and chemokines, including interleukin (IL)-6, IL-1 alpha, IL-1 beta, tu mor necrosis factor (TNF)-alpha, macrophage inflammatory protein (MIP)-1 be ta, MIP-2 beta, MIP-2 alpha, liver and activation-regulated chemokine (LARC ), MIP-1 alpha, thymus and activation-regulated chemokine (TARC), macrophag e-derived chemokine (MDC), regulated on activation, normal T cell expressed and secreted (RANTES), growth-regulated oncogene (GRO) alpha, and IL-8, we re observed in the highest inducible transcripts. Other genes encoding plas minogen activator inhibitor type 2 (PAI-2), Hc-gp39, apolipoproteins, malat e dehydrogenase, matrix metalloproteinase-9 (MMP-9), and cyclooxygenase (CO X2) were also highly elevated in LPS-stimulated monocytes. Moreover, upregu lation of Naf1 beta, IL-7 receptor, adenosine receptor A2a, and many novel genes was newly identified. These results suggest that the LPS-inducible ge ne products may be involved In cell activation and migration, angiogenesis, tissue remodeling, and metabolism, and thus may orchestrate the inflammato ry reactions. On the other hand, the expression of numerous sets of novel g enes was discovered to be down-regulated on LPS stimulation. This study rep resents the first comprehensive analysis of LPS-inducible gene expression i n human monocytes and provides tremendous novel information for the functio n of LPS-activated monocytes and targets for diagnosing, monitoring, and tr eating sepsis and various human infectious and inflammatory diseases.(Blood . 2000;96:2584-2591) (C) 2000 by The American Society of Hematology.