Document Detail


Regulation and function of epithelial secreted phospholipase A2 group X in asthma.
MedLine Citation:
PMID:  23614662     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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 sPLA2-X within the epithelium.
METHODS: We precisely phenotyped 34 patients with asthma (19 with and 15 without EIB) and 10 normal control subjects to examine in vivo differences in epithelial gene expression, quantitative morphometry 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 Pla2g10 deletion.
MEASUREMENTS AND MAIN RESULTS: We found that sPLA2-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 epithelium and directly participates in the release of arachidonic acid by epithelial cells.
CONCLUSIONS: These data reveal a relationship between epithelial-derived 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.
Authors:
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
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  American journal of respiratory and critical care medicine     Volume:  188     ISSN:  1535-4970     ISO Abbreviation:  Am. J. Respir. Crit. Care Med.     Publication Date:  2013 Jul 
Date Detail:
Created Date:  2013-07-02     Completed Date:  2013-09-12     Revised Date:  2014-07-01    
Medline Journal Info:
Nlm Unique ID:  9421642     Medline TA:  Am J Respir Crit Care Med     Country:  United States    
Other Details:
Languages:  eng     Pagination:  42-50     Citation Subset:  AIM; IM    
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Descriptor/Qualifier:
Adolescent
Adult
Animals
Asthma / genetics*,  immunology*
Asthma, Exercise-Induced / genetics,  immunology
Bronchial Hyperreactivity / genetics,  immunology
Enzyme-Linked Immunosorbent Assay / methods
Epithelial Cells / immunology*
Female
Gene Expression / genetics
Group X Phospholipases A2 / genetics*,  immunology*
Humans
Male
Mice
Mice, Inbred C57BL
Middle Aged
Real-Time Polymerase Chain Reaction / methods
Young Adult
Grant Support
ID/Acronym/Agency:
P01HL098067/HL/NHLBI NIH HHS; P51 OD011107/OD/NIH HHS; R01 HL089215/HL/NHLBI NIH HHS; R01HL089215/HL/NHLBI NIH HHS; R37 HL036235/HL/NHLBI NIH HHS; R37HL036235/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
EC 3.1.1.4/Group X Phospholipases A2
Comments/Corrections
Comment In:
Am J Respir Crit Care Med. 2013 Jul 1;188(1):2-3   [PMID:  23815713 ]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


Previous Document:  Laser Ablation in Analytical Chemistry.
Next Document:  Two substrate-confined sol-gel coassembled ordered macroporous silica structures with an open surfac...