| Asthma is a complex disease resulting from a combination of factors including genetics, environmental exposure to allergens and prior infection with respiratory viruses. A common feature of the response to allergen challenge is pattern of intense inflammation in the airways. Glucocorticoids are one of the most potent immunosuppressive and anti-inflammatory agents, and inhaled glucocorticoids is the mainstays in treatment of asthma. Classically, glucocorticoids are believed to exert their effects genomically, i.e. via occupation of cytosolic glucocorticoid receptors, translocation of the glucocoiticoid-receptor-complex into the nucleus, and subsequent activation or repression of de novo synthesis of mRNA and protein. As a result of this large array of steps, genomic effects are characterized by a time frame.However, increasing evidence suggests that the traditional theory of glucocorticoids action is not sufficient to explain the broad spectrum of glucocorticoid effects. Recently in our laboratory, it had been demonstrated that inhaled budesonide could inhibit allergic asthma reaction in guinea pigs within 10 minutes. The mechanisms by which the rapid effects is achieved are not clear. In addition to genomic effects, glucocorticoids may also exert nongenomic actions. It takes effects neither via occupation of cytosolic glucocorticoid receptors, nor the transcription of DNA and de novo synthesis of mRNA and protein. Compared with the classical genomic mechanism, the non-genomic mechanism of glucocorticoids have the following characterics: (1) It occurred instantenously after glucocorticoids exposure and with a very short latency. (2) It neither be blocked by the presense of corticosterone type n receptor antagonist RU38486, nor bythe transcription of DNA inhibitor and the protein synthesis inhibitor such as actidone and cycloheximide . (3) The bovine serum albumin-conjugated glucocorticoids which couldn't go through cell membrane within 30 min, still imitated the rapid effects of glucocorticoids.Mast cells are one of the most prominent inflammatory cell in asthma. Histamine is an important mediator released from activated mast cells provoked by allergen and has a substantial role in the pathophysiology of asthma. We supposed that the rapid inhibitory effects of glucocorticoids on the allergic asthma reaction in guinea pigs were achieved through the rapid inhibit of glucocorticoids on histamine release from mast cells. Hence we investigated the morphological evidences of glucocorticoids on the degranulation of the mast cells in allergic asthma reactions in guinea pigs and the fast actions of glucocorticoids on ovalbumin-induced histamine secretion in the model of sensitized rat peritoneal mast cells. The aim was to find out if glucocorticoids exert rapid, nongenomic effects on antigen-induced histamine secretion. Our results present the two following results.(1) Glucocorticoids exerts the rapid inhibitory effects on the degranulations of mast cells in allergic asthma reaction in guinea pigs.(2) The rapid nongenomic mechanism was involved in the inhibitory effects of glucocorticoids on antigen-induced histamine release from mast cells, which also underly the rapid inhibitory effects on allergic asthma reaction in guinea pigs. |
