TY - JOUR
T1 - DHEA-S inhibits human neutrophil and human airway smooth muscle migration
AU - Koziol-White, Cynthia J.
AU - Goncharova, Elena A.
AU - Cao, Gaoyuan
AU - Johnson, Martin
AU - Krymskaya, Vera P.
AU - Panettieri, Reynold A.
N1 - Funding Information:
This research was supported in part by funding from Epigenesis Pharmaceuticals, LLC, and the National Institutes of Health (ES013508 to RAP). Epigenesis Pharmaceuticals, LLC, contributed to the study design but had no other involvement. The National Institutes of Health had no involvement in the study.
PY - 2012/10
Y1 - 2012/10
N2 - 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.
AB - 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.
KW - Airway inflammation
KW - Airway remodeling
KW - DHEA-S
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UR - http://www.scopus.com/inward/citedby.url?scp=84864862279&partnerID=8YFLogxK
U2 - 10.1016/j.bbadis.2012.06.012
DO - 10.1016/j.bbadis.2012.06.012
M3 - Article
C2 - 22771498
AN - SCOPUS:84864862279
SN - 0925-4439
VL - 1822
SP - 1638
EP - 1642
JO - Biochimica et Biophysica Acta - Molecular Basis of Disease
JF - Biochimica et Biophysica Acta - Molecular Basis of Disease
IS - 10
ER -