Generation of Diversity in the Innate Immune System: Macrophage Heterogeneity Arises from Gene-Autonomous Transcriptional Probability of Individual Inducible Genes
Author(s)
Ravasi, Timothy
Wells, Christine
Forrest, Alistair
Underhill, David M.
Wainwright, Brandon J.
Aderem, Alan
Grimmond, Sean
Hume, David A.
Griffith University Author(s)
Year published
2002
Metadata
Show full item recordAbstract
Microbial products such as LPS stimulate macrophages to produce a wide diversity of inducible gene products needed for immediate host defense and priming of an appropriate acquired immune response. In this study, we have examined LPS-inducible gene expression in subclones of a mouse macrophage cell line, RAW264, using cDNA microarrays. Even archetypal target genes such as TNF-{alpha} were not induced in all subclones, and there was no absolute correlation between expression of pairs of genes. Nevertheless, the array analysis revealed clusters of genes that were more likely to be coexpressed. RAW264 cells stably transfected ...
View more >Microbial products such as LPS stimulate macrophages to produce a wide diversity of inducible gene products needed for immediate host defense and priming of an appropriate acquired immune response. In this study, we have examined LPS-inducible gene expression in subclones of a mouse macrophage cell line, RAW264, using cDNA microarrays. Even archetypal target genes such as TNF-{alpha} were not induced in all subclones, and there was no absolute correlation between expression of pairs of genes. Nevertheless, the array analysis revealed clusters of genes that were more likely to be coexpressed. RAW264 cells stably transfected with luciferase reporter genes driven by LPS-responsive promoters revealed the same kind of clonal heterogeneity. The results indicate that each LPS-inducible gene has its own inherent probability of activation in response to LPS.
View less >
View more >Microbial products such as LPS stimulate macrophages to produce a wide diversity of inducible gene products needed for immediate host defense and priming of an appropriate acquired immune response. In this study, we have examined LPS-inducible gene expression in subclones of a mouse macrophage cell line, RAW264, using cDNA microarrays. Even archetypal target genes such as TNF-{alpha} were not induced in all subclones, and there was no absolute correlation between expression of pairs of genes. Nevertheless, the array analysis revealed clusters of genes that were more likely to be coexpressed. RAW264 cells stably transfected with luciferase reporter genes driven by LPS-responsive promoters revealed the same kind of clonal heterogeneity. The results indicate that each LPS-inducible gene has its own inherent probability of activation in response to LPS.
View less >
Journal Title
Journal of Immunology
Volume
168
Issue
1
Publisher URI
Copyright Statement
© 2001 AAI. Self-archiving of the author-manuscript version in open access institutional repository is not yet supported by this publisher. Please refer to the journal link for access to the definitive, published version or contact the author for more information.
Subject
Immunology