Rapid nongenomic effects of glucocorticoids on allergic asthma reaction in the guinea pig

Abstract

Glucocorticoids (GCs) are routinely believed to work solely through genomic mechanisms. Recent evidence indicates that GCs can act at the membrane to exert rapid nongenomic effects on various tissues and cells. To ascertain whether nongenomic effects of GCs exist on the allergic asthma reaction, Hartley guinea pigs were sensitized with ovalbumin and challenged with the same antigen given by aerosol. Some animals received inhaled budesonide (3 mg/ml suspended in Hydroxypropyl methylcellulose vehicle) for 5 minutes before ovalbumin challenge; Other animals received saline or blank vehicle as control. We measured the changes of lung resistance and dynamic lung compliance, the pulmonary function used to evaluate allergic asthma severity. Inhaled budesonide inhibited allergic reaction within 10 minutes, which would preclude genomic-mediated responses that normally takes several hours to occur. This study infers for the first time that rapid nongenomic effect of GCs exists on allergic asthma reaction, and provides a new way to investigate nongenomic mechanism of GCs. Further study would raise the possibility of new therapeutic strategies for allergic disease including asthma.

Rapid Selective Priming of FcαR on Eosinophils by Corticosteroids

“…In these experiments, this corticosteroid could inhibit asthma symptoms within 10 min (35). We obtained data showing similar rapid effects in human asthmatics treated with fluticasone (36).…”

Anti-inflammatory effects of ivermectin in mouse model of allergic asthma

“…Mice were anesthetised by an i.p. injection of sodium pentobarbitone (50 mg/kg), and tracheotomy was performed as described [17]. The internal jugular vein was cannulated and connected to a microsyringe for intravenous methacholine administration.…”

“…The internal jugular vein was cannulated and connected to a microsyringe for intravenous methacholine administration. Airway resistance (RL, which refers to the pressure driving respiration divided by flow) and lung compliance (Cdyn, which refers to the distensibility of the lung and is defined as the change in volume of the lung produced by a change in pressure across the lung) in response to increasing concentrations of methacholine were recorded using a whole-body plethysmograph chamber (Buxco, Sharon, CT, USA) as described [17]. Results are expressed as the percentage of the respective basal values obtained from PBS-challenged negative control mice.…”

Inhibition of IRAK1 Ubiquitination Determines Glucocorticoid Sensitivity for TLR9-Induced Inflammation in Macrophages

“…The beneficial nongenomic GC effects have been implicated in asthma, allergic rhinitis, cardiovascular pathologies, and rheumatoid arthritis (7)(8)(9)(10). In fact, GC suppress aerosol-mediated allergic asthma within 10 min of challenge with allergen (11), and macrophage potency for phagocytosis and reactive oxygen species generation were inhibited within 30 min of GC treatment (12). Also, GC inhibited fMLF-induced neutrophil degranulation within 5 min of ligand treatment (13).…”