Lipopolysaccharide-inducible Gene Expression Profile in Human Monocytes.
Shin-Ichi Hashimoto1, Kei Morohoshi1, Takuji Suzuki1
1a Department of Molecular Preventive Medicine, School of Medicine The University of Tokyo Tokyo.
Scandinavian Journal of Infectious Diseases
|April 27, 2017
Summary
This study reveals the global gene expression profile of activated human monocytes using Serial Analysis of Gene Expression (SAGE). It identifies key inflammatory genes and proteins, offering new diagnostic and therapeutic targets for infectious 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 upregulation in activated human 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 uncover novel targets for diagnosing, monitoring, and treating infectious and inflammatory diseases.
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 transcripts were identified from 35,874 sequenced tags.
- Functional classification revealed 25% of inducible genes encode cytokines and chemokines, followed by metabolism, cell surface antigens, nuclear proteins, proteases, and transport proteins.
- A significant 14% of LPS-inducible genes encode proteins with unknown functions.
Conclusions:
- This study provides the first global analysis of LPS-inducible genes in human monocytes.
- The findings offer novel insights into the function of LPS-activated monocytes.
- Identified genes represent potential targets for managing sepsis and other infectious/inflammatory conditions.
