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Blood, 1 October 2000, Vol. 96, No. 7, pp. 2584-2591
PHAGOCYTES
Comprehensive gene expression profile of LPS-stimulated human
monocytes by SAGE
Takuji Suzuki,
Shin-ichi Hashimoto,
Nobuaki Toyoda,
Shigenori Nagai,
Nobuyuki Yamazaki,
Hong-Yan Dong,
Jun Sakai,
Taro Yamashita,
Toshihiro Nukiwa, and
Kouji Matsushima
From the Department of Molecular Preventive Medicine
and CREST, School of Medicine, University of Tokyo, Tokyo,
Japan; Department of Respiratory Oncology and Molecular
Medicine, Institute of Development, Aging, and Cancer, Tohoku
University, Sendai, Japan.
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-1 , IL-1 , tumor necrosis factor
(TNF)- , macrophage inflammatory protein (MIP)-1 , MIP-2 ,
MIP-2 , liver and activation-regulated chemokine (LARC), MIP-1 ,
thymus and activation-regulated chemokine (TARC), macrophage-derived chemokine (MDC), regulated on activation, normal T cell expressed and
secreted (RANTES), growth-regulated oncogene (GRO) , 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 Naf1 , 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.

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