Immune sensitization of equine bronchus: glutathione, IL-1beta expression and tissue responsiveness.
BACKGROUND
Increasing clinical epidemiological and experimental evidence indicates that excess of production of reactive oxygen free radicals (ROS) induced by an oxidative stress is involved in the pathogenesis of a number of human airway disorders, as well as equine recurrent airway obstruction. Free-radicals modulate the activation of transcription factors, such as nuclear factor-(NF)-kappaB and activator protein (AP)-1, in several different cells. This activation leads to expression of many pro-inflammatory cytokines, including interleukin (IL)-1beta. We have hypothesized that equine airway sensitization might induce an oxidative stress and increase the ROS production, which in turn might enhance a production of IL-1beta and airway hyperresponsiveness.


METHODS
We have examined the effect of passive sensitization on IL-1beta mRNA expression and electrical field stimulation (EFS)-induced contraction in equine isolated bronchi, and the potential interference of reduced-glutathione (GSH), an antioxidant, with these responses. Bronchi passively sensitized with serum from animals suffering from heaves and having high total level of IgE, and control tissues, either pretreated or not with GSH (100 microM), were used to quantify IL-1beta mRNA. Other tissues were used to study the effect of EFS (3-10-25 Hz).


RESULTS
Mean IL-1beta mRNA expression was higher in passively sensitized than in control rings. GSH significantly (p < 0.05) reduced the IL-1beta mRNA expression only in passively sensitized bronchi. ELF induced a frequency-dependent contraction in both non-sensitized and passively sensitized tissues, with a significantly greater response always observed in sensitized tissues. GSH did not modify the EFS-induced contraction in non-sensitized bronchi, but significantly (p < 0.05) decreased it in passively sensitized tissues.


CONCLUSIONS
Our data indicate that the passive sensitization of equine bronchi induces inflammation and hyperresponsiveness. These effects might be due to an oxidative stress because a pretreatment with GSH decreased the increased IL-1beta mRNA expression and responsiveness to EFS of passively sensitized bronchi.
Matera
M G
MG
Department of Experimental Medicine, 2nd University of Naples, Naples, Italy. mariagabriella.matera@unina2.it
Calzetta
L
L
Peli
A
A
Scagliarini
A
A
Matera
C
C
Cazzola
M
M
D000818:Animals; D001980:Bronchi / Q000276:immunology* / Q000473:pathology; D005786:Gene Expression Regulation / Q000276:immunology; D005978:Glutathione / Q000276:immunology*; D006734:Horse Diseases / Q000276:immunology* / Q000473:pathology; D006736:Horses; D007114:Immunization / Q000379:methods* / Q000662:veterinary*; D066298:In Vitro Techniques; D007375:Interleukin-1 / Q000276:immunology*; D008297:Male; D017382:Reactive Oxygen Species / Q000276:immunology; D012130:Respiratory Hypersensitivity / Q000276:immunology / Q000473:pathology / Q000662:veterinary*
D007375:Interleukin-1; D017382:Reactive Oxygen Species; D005978:Glutathione