Regulation and function of epithelial secreted phospholipase A2 group X in asthma

Teal S. Hallstrand, Ying Lai, William A. Altemeier, Cara L. Appel, Brian Johnson, Charles W. Frevert, Kelly L. Hudkins, James G. Bollinger, Prescott G. Woodruff, Dallas M. Hyde, William R. Henderson, Michael H. Gelb

Research output: Contribution to journalArticle

26 Scopus citations

Abstract

Rationale: Indirect airway hyperresponsiveness (AHR) is a fundamental feature of asthma that is manifest as exercise-induced bronchoconstriction (EIB). Secreted phospholipase A2 group X (sPLA2-X) plays a key role in regulating eicosanoid formation and the development of inflammation and AHR in murine models. Objectives: We sought to examine sPLA2-X in the airway epithelium and airway wall of patients with asthma, the relationship to AHR in humans, and the regulation and function of sPLA 2-X within the epithelium. Methods:We precisely phenotyped 34 patients with asthma (19 with and15 without EIB)and10 normal control subjects to examinein vivo differences in epithelial gene expression, quantitativemorphometry of endobronchial biopsies, and levels of secreted protein. The regulation of sPLA2-X gene (PLA2G10) expression was examined in primary airway epithelial cell cultures. The function of epithelial sPLA2-X in eicosanoid formation was examined using PLA2 inhibitors and murine tracheal epithelial cells with PlA 2g10 deletion. Measurements and Main Results: We found that sPLA 2-X protein is increased in the airways of patients with asthma and that epithelial-derived sPLA2-X may be increased in association with indirect AHR. The expression of sPLA2-X increases during in vitro epithelial differentiation; is regulated by inflammatory signals including tumor necrosis factor, IL-13, and IL-17; and is both secreted from the epitheliumand directly participates in the release of arachidonic acid by epithelial cells. Conclusions: These data reveal a relationship between epithelialderived sPLA2-X and indirect AHR in asthma and that sPLA2-X serves as an epithelial regulator of inflammatory eicosanoid formation. Therapies targeting epithelial sPLA2-X may be useful in asthma.

Original languageEnglish (US)
Pages (from-to)42-50
Number of pages9
JournalAmerican Journal of Respiratory and Critical Care Medicine
Volume188
Issue number1
DOIs
StatePublished - Jul 1 2013

Keywords

  • Airway hyperresponsiveness
  • Asthma
  • Eicosanoid
  • Epithelial cell
  • Secretory phospholipase A

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine
  • Critical Care and Intensive Care Medicine

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    Hallstrand, T. S., Lai, Y., Altemeier, W. A., Appel, C. L., Johnson, B., Frevert, C. W., Hudkins, K. L., Bollinger, J. G., Woodruff, P. G., Hyde, D. M., Henderson, W. R., & Gelb, M. H. (2013). Regulation and function of epithelial secreted phospholipase A2 group X in asthma. American Journal of Respiratory and Critical Care Medicine, 188(1), 42-50. https://doi.org/10.1164/rccm.201301-0084OC