Glucocorticoids ameliorate antigen-induced bronchial smooth muscle hyperresponsiveness by inhibiting upregulation of RhoA in rats.
ABSTRACT To determine the mechanism(s) of the inhibitory effect of glucocorticoids on airway hyperresponsiveness in allergic bronchial asthma, the effects of systemic treatment with glucocorticoids on bronchial smooth muscle hyperresponsiveness and RhoA upregulation were investigated in rats with allergic bronchial asthma. Rats were sensitized and repeatedly challenged with 2,4-dinitrophenylated Ascaris suum antigen. Animals were also treated with prednisolone or beclomethasone (each 10 mg/kg, i.p.) once a day during the antigen inhalation period. Repeated antigen inhalation caused a marked bronchial smooth muscle hyperresponsiveness to acetylcholine with an upregulation of RhoA. Augmented acetylcholine-induced activation of RhoA and phosphorylation of myosin light chain were observed in bronchial smooth muscles of the antigen-exposed animals. Systemic treatment with either glucocorticoid used inhibited the bronchial smooth muscle hypercontraction until the level of the sensitized control rats that received saline inhalation instead of antigen challenge. Interestingly, both glucocorticoids also inhibited the upregulation of RhoA and augmented acetylcholine-induced activation of RhoA and phosphorylation of myosin light chain. In conclusion, glucocorticoids ameliorated the augmented bronchial smooth muscle contraction by inhibiting upregulation of RhoA. These effects of glucocorticoids may account for, in part, their beneficial effects in the treatment of asthma.
Article: The influence of dexamethasone and the role of some antioxidant vitamins in the pathogenesis of experimental bronchial asthma[show abstract] [hide abstract]
ABSTRACT: Background: Bronchial asthma is a disease characterized by paroxysmal and reversible obstruction of the airways. The imbalance between the oxidant and antioxidant system that is called oxidative stress is critical in asthma pathogenesis. It is likely, therefore, that antioxidants may be effective in the treatment of asthma. Systemic treatment with glucocorticoids has been reported to inhibit smooth muscle hypercontraction which may account partially for their beneficial effects in the treatment of asthma. Objective: The present study was conducted in order to study the effect of dexamethasone and some antioxidant vitamins on interleukin-4 (IL-4), immunoglobulin E (IgE) and heat shock protein 70 (Hsp70) in bronchial asthma in rats, and to recognize their possible beneficial role. Method: The study was conducted on 60 adult male albino rats randomly divided into 4 groups (15 for each group): including normal control group (group A); asthma model group where rats were sensitized by ovalbumin and challenged with antigen aerosol producing bronchial asthma (group B); asthma model group treated with antioxidant vitamins (vitamin E and vitamin C) (group C); asthma model group treated with dexamethasone (group D). Blood and lung samples were collected from all groups. Results and Conclusion: Our results revealed a significant decrease of serum reduced glutathione (GSH) levels among groups B, C and D as compared to group A, while there was a significant increase in group C and D as compared to group B. Antioxidant and dexametha-sone treatment resulted in a significant decrease of serum IL-4, malondialdehyde (MDA), and serum IgE levels in group C and D as compared to group B. Antioxidant treatment resulted in a significant decrease of serum Hsp70 level as compared to group B, while dexamethasone treatment resulted in a significant increase of serum Hsp70 level as compared to group B. This study suggests that it is likely that a combination of antioxidant vitamins may be effective in the treatment of asthma, considering their reported effects on lowering MDA, IL-4, and IgE levels, and the similar beneficial effects of dexamethasone in addition to increasing the expression of Hsp70 in the studied model of bronchial asthma.Journal of Experimental Pharmacology. 01/2010; 2:93-103.
03/2012; , ISBN: 978-953-51-0180-2