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Lipopolysaccharide-inducible gene expression profile in human monocytes
Shin-Ichi Hashimoto1, Kei Morohoshi, Takuji Suzuki
1Department of Molecular Preventive Medicine, School of Medicine, The University of Tokyo, Tokyo, Japan.
Scandinavian Journal of Infectious Diseases
|November 19, 2003
Summary
This study globally analyzed gene expression in lipopolysaccharide (LPS)-stimulated human monocytes using Serial Analysis of Gene Expression (SAGE). It identified numerous LPS-inducible genes, offering new insights into monocyte function and potential targets for infectious and inflammatory diseases.
Area of Science:
- Immunology
- Molecular Biology
- Genomics
Background:
- Monocytes/macrophages are crucial for host defense, phagocytosis, antigen presentation, and inflammatory mediator production.
- While gene and protein up-regulation in activated monocytes is known, a comprehensive understanding of their pathophysiological roles is lacking.
Purpose of the Study:
- To perform a global analysis of gene expression in lipopolysaccharide (LPS)-stimulated human monocytes.
- To identify and functionally classify LPS-inducible genes in monocytes.
- To provide novel information on the function of LPS-activated monocytes for disease diagnosis and treatment.
Main Methods:
- Serial Analysis of Gene Expression (SAGE) and Long SAGE were employed on LPS-stimulated human monocytes.
- Gene expression profiles of stimulated monocytes were compared to resting monocytes.
- LPS-inducible genes (≥ 8-fold increase) were functionally classified.
Main Results:
- Over 12,000 different transcripts were identified from 35,874 sequenced tags.
- Key functional categories of LPS-inducible genes included cytokines/chemokines (25%), metabolism-related proteins (11%), and cell surface antigens (9%).
- A significant portion (14%) of LPS-inducible genes encoded proteins with unknown functions.
Conclusions:
- This study presents the first global gene expression analysis of LPS-inducible genes in human monocytes.
- The findings offer substantial new information regarding the function of LPS-activated monocytes.
- Identified genes may serve as targets for diagnosing, monitoring, and treating sepsis and other infectious/inflammatory diseases.