title: Beta-2-receptor regulation of immunomodulatory proteins in airway smooth muscle.
abstract: Airway smooth muscle (ASM) cells have been shown to secrete significant amounts of immunomodulatory factors (IMFs), many of which are typically ascribed to trafficking leukocytes (e.g., GM-CSF, IL-6, IL-13, and eotaxin), and may be indicative of an immunomodulatory role for ASM in control of airway function, as well as in airway diseases states associated with acute and/or chronic inflammation, such as asthma and COPD. Furthermore, epinephrine analogues such as albuterol, which ligate the G-protein coupled beta-2-receptor and have been clinically applied to promote ASM relaxation and bronchodilation in the treatment of asthma and COPD, also have been reported to downregulate IMF release by ASM, both individually and in additive fashion, in combination with corticosteroids. Based on experimental data, an inverse agonist/agonist model is proposed to explain these behaviors modeled on cell stimulatory states and G-protein coupled receptor activation. The ramifications of the model are considered in light of unexplained paradoxical clinical findings, and may provide a model for the understanding of beta-2-receptor agonist modulation of airway inflammation and function.
authors.affiliation: Department of Internal Medicine, Division of Pulmonary, Allergy, and Critical Care Medicine, University of Texas Medical Branch, 301 University Boulevard, Galveston, TX 77555-1083, USA. Bill.Ameredes@utmb.edu
authors.forename: Bill T
authors.initials: BT
authors.lastname: Ameredes
mesh_terms: D058666:Adrenergic beta-2 Receptor Agonists / Q000494:pharmacology; D000420:Albuterol / Q000494:pharmacology; D001993:Bronchodilator Agents / Q000494:pharmacology; D016207:Cytokines / Q000276:immunology; D006801:Humans; D008954:Models, Biological; D009130:Muscle, Smooth / Q000187:drug effects / Q000276:immunology*; D018343:Receptors, Adrenergic, beta-2 / Q000276:immunology*; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism; D012137:Respiratory System / Q000187:drug effects / Q000276:immunology*
chemical_list: D058666:Adrenergic beta-2 Receptor Agonists; D001993:Bronchodilator Agents; D016207:Cytokines; D018343:Receptors, Adrenergic, beta-2; D043562:Receptors, G-Protein-Coupled; D000420:Albuterol