Identification of High and Low Responders to Lipopolysaccharide in Normal Subjects: An Unbiased Approach to Identify Modulators of Innate Immunity
Abstract
LPS stimulates a vigorous inflammatory response from circulating leukocytes that varies greatly from individual to individual. The goal of this study was to use an unbiased approach to identify differences in gene expression that may account for the high degree of interindividual variability in inflammatory responses to LPS in the normal human population. We measured LPS-induced cytokine production ex vivo in whole blood from 102 healthy human subjects and identified individuals who consistently showed either very high or very low responses to LPS (denoted lpshigh and lpslow, respectively). Comparison of gene expression profiles between the lpshigh and lpslow individuals revealed 80 genes that were differentially expressed in the presence of LPS and 21 genes that were differentially expressed in the absence of LPS (p < 0.005, ANOVA). Expression of a subset of these genes was confirmed using real-time RT-PCR. Functional relevance for one gene confirmed to be expressed at a higher level in lpshigh, adipophilin, was inferred when reduction in adipophilin mRNA by small interfering RNA in the human monocyte-like cell line THP-1 resulted in a modest but significant reduction in LPS-induced MCP-1 mRNA expression. These data illustrate a novel approach to the identification of factors that determine interindividual variability in innate immune inflammatory responses and identify adipophilin as a novel potential regulator of LPS-induced MCP-1 production in human monocytes.
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Recent studies have shown a vast amount of variability in the innate immune responses of healthy humans, as reflected by the intermediate phenotype of whole-blood cytokine responses to bacterial products.
“Recent stud- ies have shown a vast amount of variability in the innate immune responses of healthy humans, as reflected by the intermediate phenotype of whole-blood cytokine responses to bacterial products (151).”
From Into the Eye of the Cytokine Storm (2012) · cites this paper as [151]
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Into the Eye of the Cytokine Storm
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Self-citationEffect of age on chronic inflammation and responsiveness to bacterial and viral challenges
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- Authors
- Wurfel, M. M., Park, W. Y., Radella, F., Ruzinski, J., Sandstrom, A., Strout, J., Bumgarner, R. E., & Martin, T. R.
- Affiliations
- University of Washington (US)
- Venue
- The Journal of Immunology
- Publisher
- Oxford University Press (OUP)
- Published
- 2005-08
- Volume
- 175
- Issue
- 4
- Pages
- 2570-2578
- ISSN
- 0022-1767 (ISSN-L)
- 1550-6606
- OpenAlex
- W1861696557
- Cited by
- 130
- References
- 64
- Citations by year
- 2026: 3 · 2024: 7 · 2023: 1 · 2022: 5 · 2021: 6 · 2020: 9 · 2019: 3 · 2018: 2 · 2017: 5 · 2016: 7 · 2015: 6 · 2014: 7 · 2013: 9 · 2012: 10
- FWCI
- 2.60
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- The Journal of Immunology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- U.S. Public Health Service (K23 62-9063)
- National Heart, Lung, and Blood Institute (P50HL073996)
- National Institute of Allergy and Infectious Diseases (U54AI057141)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
- Health Sciences › Medicine › Epidemiology › Adipokines, Inflammation, and Metabolic Diseases
- Life Sciences › Immunology and Microbiology › Immunology › Immune responses and vaccinations
- Keywords
- lipopolysaccharide, innate immunity, interindividual variability, cytokine production, gene expression profiling, adipophilin, MCP-1, monocytes, THP-1 cells, siRNA knockdown, inflammation
- MeSH terms
- Perilipin-2, Adolescent, Adult, Aged, Analysis of Variance, Dose-Response Relationship, Immunologic, Female, Humans, Immunity, Innate, Lipopolysaccharides, Male, Membrane Proteins, Middle Aged, RNA, Messenger, Immunophenotyping, Cytokines, Inflammation Mediators, Chemokine CCL2, Gene Expression Profiling, Cell Line, Tumor
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