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Key Role of Group V Secreted Phospholipase A2 in Th2 Cytokine and Dendritic Cell-Driven Airway Hyperresponsiveness and Remodeling
- Source :
- PLoS ONE, Vol 8, Iss 2, p e56172 (2013), PLoS ONE
- Publication Year :
- 2013
- Publisher :
- Public Library of Science (PLoS), 2013.
-
Abstract
- Background Previous work has shown that disruption of the gene for group X secreted phospholipase A2 (sPLA2-X) markedly diminishes airway hyperresponsiveness and remodeling in a mouse asthma model. With the large number of additional sPLA2s in the mammalian genome, the involvement of other sPLA2s in the asthma model is possible – in particular, the group V sPLA2 (sPLA2-V) that like sPLA2-X is highly active at hydrolyzing membranes of mammalian cells. Methodology and Principal Findings The allergen-driven asthma phenotype was significantly reduced in sPLA2-V-deficient mice but to a lesser extent than observed previously in sPLA2-X-deficient mice. The most striking difference observed between the sPLA2-V and sPLA2-X knockouts was the significant impairment of the primary immune response to the allergen ovalbumin (OVA) in the sPLA2-V−/− mice. The impairment in eicosanoid generation and dendritic cell activation in sPLA2-V−/− mice diminishes Th2 cytokine responses in the airways. Conclusions This paper illustrates the diverse roles of sPLA2s in the immunopathogenesis of the asthma phenotype and directs attention to developing specific inhibitors of sPLA2-V as a potential new therapy to treat asthma and other allergic disorders.
- Subjects :
- CD4-Positive T-Lymphocytes
Anatomy and Physiology
Pulmonology
Respiratory System
lcsh:Medicine
Polymerase Chain Reaction
Group V Phospholipases A2
Mice
0302 clinical medicine
Immune Physiology
Molecular Cell Biology
lcsh:Science
Immune Response
Mice, Knockout
0303 health sciences
Multidisciplinary
Allergy and Hypersensitivity
respiratory system
Immunohistochemistry
3. Good health
Medicine
Cellular Types
medicine.symptom
Research Article
Ovalbumin
Immune Cells
Immunology
Inflammation
Immunopathology
Biology
03 medical and health sciences
Th2 Cells
Phospholipase A2
medicine
Animals
Group X Phospholipases A2
Gene knockout
030304 developmental biology
Asthma
lcsh:R
Dendritic cell
medicine.disease
respiratory tract diseases
Disease Models, Animal
Eicosanoid
Immune System
biology.protein
Clinical Immunology
lcsh:Q
030215 immunology
Subjects
Details
- ISSN :
- 19326203
- Volume :
- 8
- Database :
- OpenAIRE
- Journal :
- PLoS ONE
- Accession number :
- edsair.doi.dedup.....18b85e2b71181f8f523a9cdcfb347acf