Agonist-specific patterns of beta 2-adrenoceptor responses in human airway cells during prolonged exposure.

Background And Purpose: Beta(2)-adrenoceptor agonists (beta(2)-agonists) are important bronchodilators used in the treatment of asthma and chronic obstructive pulmonary disease. At the molecular level, beta(2)-adrenergic agonist stimulation induces desensitization of the beta(2)-adrenoceptor. In this study, we have examined the relationships between initial effect and subsequent reduction of responsiveness to restimulation for a panel of beta(2)-agonists in cellular and in vitro tissue models.

Differences in endogenous esterification and retention in the rat trachea between budesonide and ciclesonide active metabolite.

The airway retention of inhaled glucocorticosteroids (GCs) depends largely on their lipophilicity. Inhaled budesonide (BUD) becomes highly lipophilic reversibly by the formation of esters acting as a reservoir of active BUD. Ciclesonide (CIC) was also reported to form esters after hydrolysis to active metabolite (CIC-AM).

Cooperative inhibitory effects of budesonide and formoterol on eosinophil superoxide production stimulated by bronchial epithelial cell conditioned medium.

Background: Improved asthma control by combinations of inhaled glucocorticosteroids (GCs) and long-acting beta(2)-agonists (LABAs) includes a reduced frequency and severity of exacerbations. In view of the association of exacerbations with increased airway inflammation, the question has arisen as to whether LABAs are able to complement the known anti-inflammatory activity of GCs. To address this, we studied the effects of a LABA, formoterol (FORM), and a GC, budesonide (BUD), alone and in combination, on bronchial epithelial cell-mediated eosinophil superoxide production in vitro.

Nitric oxide represses inhibitory kappaB kinase through S-nitrosylation.

Nitric oxide (NO) possesses antiinflammatory effects, which may be exerted via its ability to inhibit the transcription factor, NF-kappaB. A commonly proposed mode of action for inhibition of NF-kappaBbyNO involves interference with NF-kappaB binding to DNA. Because activation of inhibitory kappaB kinase (IKK), the prerequisite enzyme complex necessary to induce NF-kappaB, is subject to redox regulation, we assessed whether IKK could present a more proximal target for NO to inhibit NF-kappaB activation.

Reactive nitrogen species and cell signaling: implications for death or survival of lung epithelium.

Reactive nitrogen species such as nitric oxide, peroxynitrite, and nitrogen dioxide have been implicated in the pathophysiology of inflammatory lung diseases. Yet, the molecular mechanisms and cell signaling events responsible for cellular injury remain to be elucidated. Two major signaling pathways, co-ordinately regulated and responsible for cell survival and cell death, involve nuclear factor kappa B and c-Jun-N-terminal kinase, respectively.