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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
Author(s) -
Weber Patty S. D.,
Toelboell Trine,
Chang LingChu,
Tirrell Janelle Durrett,
Saama Peter M.,
Smith George W.,
Burton Jeanne L.
Publication year - 2004
Publication title -
journal of leukocyte biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.819
H-Index - 191
eISSN - 1938-3673
pISSN - 0741-5400
DOI - 10.1189/jlb.1003505
Subject(s) - biology , glucocorticoid , gene expression , l selectin , gene , immunology , p selectin , regulation of gene expression , endocrinology , medicine , microbiology and biotechnology , genetics , cell adhesion molecule , platelet , platelet activation
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.