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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-1alpha , IL-1beta , tumor necrosis factor (TNF)-alpha , macrophage inflammatory protein (MIP)-1beta , MIP-2beta , MIP-2alpha , liver and activation-regulated chemokine (LARC), MIP-1alpha , thymus and activation-regulated chemokine (TARC), macrophage-derived chemokine (MDC), regulated on activation, normal T cell expressed and secreted (RANTES), growth-regulated oncogene (GRO) alpha , 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 Naf1beta , 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.

© 2000 by The American Society of Hematology.
 

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