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Mechanisms of glucocorticoid-induced down-regulation of neutrophil L-selectin in cattle: evidence for effects at the gene-expression level and primarily on blood neutrophils
Abstract
One anti-inflammatory action of glucocorticoids is down-regulation of surface L-selectin on circulating neutrophils. However, it is unclear if this is a result of release of affected bone marrow neutrophils or if the steroid has direct effects on L-selectin expression in existing blood neutrophils. We recently demonstrated that circulating neutrophils from cattle with high blood concentrations of endogenous glucocorticoid had reduced L-selectin mRNA, suggesting that the steroid interrupted L-selectin gene expression. In the current study, dexamethasone (DEX) was administered to cattle in vivo, and blood and bone marrow neutrophils were studied simultaneously within the animal to determine which pool of cells responds to glucocorticoids with inhibited L-selectin expression. Purified blood neutrophils were also treated with DEX ± RU486 in vitro, and glucocorticoid effects on L-selectin expression were determined. Our results indicate that glucocorticoid-induced suppression of L-selectin, which accompanies neutrophilia, is likely mediated by direct effects of glucocorticoid receptor activation on intracellular reservoirs of L-selectin mRNA and protein in cattle, predominantly in blood neutrophils.
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“Another salient outcome of GCs administration is neutrophilia. The steroid hormone expands the number of circulating neutrophils by (1) increasing their egress from the bone-marrow to the bloodstream and by (2) concomitantly hindering their transmigration to inflammatory sites by alleviating the expression of cell adhesion molecules (43, 44).”
From The HPA – Immune Axis and the Immunomodulatory Actions of Glucocorticoids in the Brain (2014) · cites this paper as [44]
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Metadata
- Authors
- Weber, P. S. D., Toelboell, T., Chang, L.-C., Tirrell, J. D., Saama, P. M., Smith, G. W., & Burton, J. L.
- Affiliations
- Immunogenetics Laboratory , East Lansing
- Michigan State University (US)
- Corresponding author
- Burton, Jeanne L
- ORCID
- Chang, Ling-Chu
- Venue
- Journal of Leukocyte Biology
- Publisher
- Oxford University Press (OUP)
- Published
- 2004-02-03
- Volume
- 75
- Issue
- 5
- Pages
- 815-827
- ISSN
- 0741-5400 (ISSN-L)
- 1938-3673
- OpenAlex
- W2162667045
- Cited by
- 113
- References
- 62
- Citations by year
- 2025: 1 · 2023: 3 · 2022: 4 · 2021: 7 · 2020: 15 · 2019: 4 · 2018: 10 · 2017: 5 · 2016: 7 · 2015: 1 · 2014: 5 · 2013: 4 · 2012: 8
- FWCI
- 3.56
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Leukocyte Biology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- USDA-NRI (#01-35204-10798)
- Michigan Agricultural Experiment Station (#MICL 01836)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Endocrinology › Estrogen and related hormone effects
- Health Sciences › Medicine › Immunology and Allergy › Cell Adhesion Molecules Research
- Life Sciences › Immunology and Microbiology › Immunology › Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Keywords
- glucocorticoids, L-selectin, neutrophils, cattle, dexamethasone, glucocorticoid receptor, gene expression regulation, neutrophilia, bone marrow neutrophils, anti-inflammatory activity, RU486, mRNA expression
- MeSH terms
- Animals, Blood Cells, Cattle, Dexamethasone, Glucocorticoids, Neutrophils, Receptors, Glucocorticoid, RNA, Messenger, Transcription, Genetic, Down-Regulation, L-Selectin
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