Time-dependent alterations in gene expression of interleukin-8 in the bronchial epithelium of horses with recurrent airway obstruction.
OBJECTIVE
To evaluate time-dependent alterations in gene expression of chemokines in bronchial epithelium of recurrent airway obstruction (RAO)-affected horses and whether alterations resulted from increases in gene expression of interleukin (IL)-17 in cells isolated from bronchoalveolar lavage fluid (BALF).


METHODS
8 RAO-susceptible horses and 9 control horses.


METHODS
In 2 experiments, both groups of horses were evaluated after being maintained on pasture and after being stabled and fed dusty hay for 1, 14, 35, and 49 days (experiment 1) or 14 and 28 days (experiment 2). In experiment 1, gene expression of IL-8, chemokine (C-X-C motif) ligand 1 (CXCL1), granulocyte-macrophage colony-stimulating factor (GM-CSF), granulocyte colony-stimulating factor (G-CSF), and Toll-like receptor 4 (TLR4) in epithelium and IL-8, IL-17, and TLR4 in BALF cells was measured. In experiment 2, bronchial biopsy specimens were evaluated for IL-8 immunoreactivity.


RESULTS
In RAO-susceptible horses after 14 days of challenge exposure, there was a 3- and 10-fold increase in gene expression of IL-8 for epithelial and BALF cells and an increase in IL-8 immunoreactivity in epithelial cells. Challenge exposure failed to alter gene expression of CXCL1, GM-CSF, G-CSF, and TLR4 in epithelial cells of any horses at any time point. During challenge exposure, gene expression of BALF cell IL-17 was downregulated in control horses (day 1) and upregulated in RAO-affected horses (day 35).


CONCLUSIONS
Epithelial-derived IL-8 may promote airway neutrophilia, but the inciting stimulus is unlikely to be IL-17 because upregulation of this gene is subsequent to that of IL-8 in epithelial cells.
Department of Clinical Sciences, College of Veterinary Medicine, Cornell University, Ithaca, NY 14853, USA.
Dorothy M
DM
Ainsworth
Bettina
B
Wagner
Marco
M
Franchini
Gabriele
G
Grünig
Hollis N
HN
Erb
Jean-Yin
JY
Tan
D000402:Airway Obstruction / Q000276:immunology / Q000662:veterinary*; D000821:Animal Feed; D000818:Animals; D001980:Bronchi / Q000276:immunology; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D004198:Disease Susceptibility / Q000662:veterinary; D005786:Gene Expression Regulation; D006734:Horse Diseases / Q000276:immunology*; D006736:Horses; D016209:Interleukin-8 / Q000235:genetics*; D007958:Leukocyte Count / Q000662:veterinary; D018655:Lymphocyte Count / Q000662:veterinary; D012008:Recurrence; D020545:Respiratory Mucosa / Q000276:immunology*
D016209:Interleukin-8