DHEA-S inhibits human neutrophil and human airway smooth muscle migration

Cynthia J. Koziol-White, Elena A. Goncharova, Gaoyuan Cao, Martin Johnson, Vera P. Krymskaya, Reynold Panettieri

Research output: Contribution to journalArticlepeer-review

20 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)1638-1642
Number of pages5
JournalBiochimica et Biophysica Acta - Molecular Basis of Disease
Volume1822
Issue number10
DOIs
StatePublished - Oct 2012
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Molecular Medicine
  • Molecular Biology

Keywords

  • Airway inflammation
  • Airway remodeling
  • DHEA-S

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