Title: DHEA-S inhibits human neutrophil and human airway smooth muscle migration.
Authors: Koziol-White, Cynthia J; Goncharova, Elena A; Cao, Gaoyuan; Johnson, Martin; Krymskaya, Vera P; Panettieri Jr, Reynold A
Published In Biochim Biophys Acta, (2012 Oct)
Abstract: Airway diseases such as asthma, emphysema, and chronic bronchitis are, in part, characterized by reversible airflow obstruction and inflammation. In severe disease, marked decreases in lung function are associated with airway smooth muscle proliferation and airway neutrophilia. Inhaled glucocorticoids attenuate increased airflow obstruction and airway inflammation that occur, in part, due to increased smooth muscle migration and proliferation, as well as the airway neutrophilia. Glucocorticoids, however, have adverse side effects and, in some patients, are ineffective despite high doses. Recent research has explored the effects of non-traditional steroids on attenuation of inflammation associated with airway diseases. These non-traditional steroids have improved side effect profiles in comparison to glucocorticoid therapy. Our studies assessed effects of dehydroepiandrosterone-3-sulfate (DHEA-S) on migration of both human peripheral blood neutrophils (PMN) and human airway smooth muscle cells (HASM). DHEA-S dose-dependently inhibited chemotaxis of PMN and HASM while having no effect on the phosphorylation levels of Akt, ERK1/2, p38 MAPK or PKC, canonical positive regulators of cell migration. These studies demonstrate direct effects of DHEA-S on cell migration, thereby suggesting that DHEA-S may attenuate airway inflammation and cell migration.
PubMed ID: 22771498
MeSH Terms: Cell Movement/drug effects*; Cells, Cultured; Dehydroepiandrosterone Sulfate/pharmacology*; Glucocorticoids/pharmacology; Humans; MAP Kinase Signaling System/drug effects; Muscle, Smooth/cytology; Muscle, Smooth/drug effects*; Muscle, Smooth/metabolism; Myocytes, Smooth Muscle/cytology; Myocytes, Smooth Muscle/drug effects*; Myocytes, Smooth Muscle/metabolism; Neutrophils/cytology; Neutrophils/drug effects*; Neutrophils/metabolism; Phosphorylation/drug effects; Platelet-Derived Growth Factor/metabolism; Protein Kinase C/metabolism; Proto-Oncogene Proteins c-akt/metabolism; Respiratory System/drug effects; Respiratory System/metabolism; p38 Mitogen-Activated Protein Kinases/metabolism