Format

Send to

Choose Destination
Vet Immunol Immunopathol. 2009 Mar 15;128(1-3):126-31. doi: 10.1016/j.vetimm.2008.10.303. Epub 2008 Oct 17.

Genomic and non-genomic effects of dexamethasone on equine peripheral blood neutrophils.

Author information

1
Department of Clinical Sciences, Faculty of Veterinary Medicine, Université de Montréal, 3200 Sicotte, Saint-Hyacinthe, Québec, Canada J2S 7C6.

Abstract

BACKGROUND:

Glucocorticoids have potent anti-inflammatory properties and are frequently used for the treatment of domestic animal species, including horses. They induce a down-regulation of multiple inflammatory pathways through both genomic and non-genomic effects. Currently, little is known on the effects of glucocorticoids on equine peripheral blood neutrophils.

HYPOTHESIS:

Dexamethasone (DEX), a potent synthetic glucocorticoid, inhibits the functions of equine peripheral blood neutrophils through both genomic and non-genomic effects.

ANIMALS:

Six healthy adult mixed breed female horses.

METHODS:

To assess the genomic effects of DEX, peripheral blood neutrophils were isolated using a gradient technique and incubated 6 h with 100 ng/ml LPS and 10(-6) M DEX alone, or combined with the glucocorticoid receptor (GR) inhibitor RU486 (10(-5) M). Messenger RNA for IL-8, TNF-alpha and TLR-4 were measured using real-time RT-PCR. The non-genomic effects of DEX were studied in neutrophils incubated with 5 microM dichlorodihydrofluorescein (DCF) and 10(-6) M DEX 5, 10 and 15 min prior to being stimulated with 5 ng/ml phorbol myristate acetate. Neutrophils were similarly co-incubated with DEX (10(-6) M, 15 min) and RU486 (10(-5) M) to evaluate the contribution of the GR to these effects. The oxidation of DCF was studied using flow-cytometry.

RESULTS:

Neutrophils stimulation with LPS resulted in a significant increase in IL-8, TNF-alpha and TLR-4 mRNA expressions (p<0.0001); incubation with DEX significantly down-regulated this process (p<0.0001). DEX significantly reduced oxidation of DCF after 10 and 15 min of incubation (p<0.0001). Those effects were mediated through the GRs.

CONCLUSION:

DEX exerts anti-inflammatory effects on equine peripheral blood neutrophils through both genomic and non-genomic pathways.

PMID:
19036458
DOI:
10.1016/j.vetimm.2008.10.303
[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center