Key role of group v secreted phospholipase A2 in Th2 cytokine and dendritic cell-driven airway hyperresponsiveness and remodeling
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...
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| Veröffentlicht in: | PloS one 2013-02, Vol.8 (2), p.e56172-e56172 |
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| creator | Henderson, Jr, William R Ye, Xin Lai, Ying Ni, Zhanglin Bollinger, James G Tien, Ying-Tzang Chi, Emil Y Gelb, Michael H |
| description | 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.
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.
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. |
| doi_str_mv | 10.1371/journal.pone.0056172 |
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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.
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.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0056172</identifier><identifier>PMID: 23451035</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Acids ; Allergens ; Allergies ; Animals ; Antigens ; Asthma ; Asthma - enzymology ; Asthma - genetics ; Asthma - immunology ; Biology ; Biosynthesis ; CD4-Positive T-Lymphocytes - metabolism ; Cell activation ; Cytokines ; Dendritic cells ; Disease Models, Animal ; Enzymes ; Genomes ; Group V Phospholipases A2 - genetics ; Group V Phospholipases A2 - metabolism ; Group X Phospholipases A2 - genetics ; Group X Phospholipases A2 - metabolism ; Immune response ; Immune system ; Immunohistochemistry ; Immunopathogenesis ; Impairment ; Inflammation ; Kinases ; Lymphocytes T ; Mammalian cells ; Mammals ; Medicine ; Membranes ; Mice ; Mice, Knockout ; Neutrophils ; Ovalbumin ; Ovalbumin - immunology ; Phospholipase ; Phospholipase A2 ; Polymerase Chain Reaction ; Remodeling ; Respiratory tract ; Studies ; Th2 Cells - metabolism</subject><ispartof>PloS one, 2013-02, Vol.8 (2), p.e56172-e56172</ispartof><rights>2013 Henderson et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License: https://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2013 Henderson et al 2013 Henderson et al</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c5072-7ffc06968dc4ea4c67ddf873bce3682def10a3ce4fb95d40b394604bafca49253</citedby><cites>FETCH-LOGICAL-c5072-7ffc06968dc4ea4c67ddf873bce3682def10a3ce4fb95d40b394604bafca49253</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3581544/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3581544/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,860,881,2096,2915,23845,27901,27902,53766,53768,79569,79570</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/23451035$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Henderson, Jr, William R</creatorcontrib><creatorcontrib>Ye, Xin</creatorcontrib><creatorcontrib>Lai, Ying</creatorcontrib><creatorcontrib>Ni, Zhanglin</creatorcontrib><creatorcontrib>Bollinger, James G</creatorcontrib><creatorcontrib>Tien, Ying-Tzang</creatorcontrib><creatorcontrib>Chi, Emil Y</creatorcontrib><creatorcontrib>Gelb, Michael H</creatorcontrib><title>Key role of group v secreted phospholipase A2 in Th2 cytokine and dendritic cell-driven airway hyperresponsiveness and remodeling</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>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.
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.
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.</description><subject>Acids</subject><subject>Allergens</subject><subject>Allergies</subject><subject>Animals</subject><subject>Antigens</subject><subject>Asthma</subject><subject>Asthma - enzymology</subject><subject>Asthma - genetics</subject><subject>Asthma - immunology</subject><subject>Biology</subject><subject>Biosynthesis</subject><subject>CD4-Positive T-Lymphocytes - metabolism</subject><subject>Cell activation</subject><subject>Cytokines</subject><subject>Dendritic cells</subject><subject>Disease Models, Animal</subject><subject>Enzymes</subject><subject>Genomes</subject><subject>Group V Phospholipases A2 - genetics</subject><subject>Group V Phospholipases A2 - metabolism</subject><subject>Group X Phospholipases A2 - genetics</subject><subject>Group X Phospholipases A2 - 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enzymology</topic><topic>Asthma - genetics</topic><topic>Asthma - immunology</topic><topic>Biology</topic><topic>Biosynthesis</topic><topic>CD4-Positive T-Lymphocytes - metabolism</topic><topic>Cell activation</topic><topic>Cytokines</topic><topic>Dendritic cells</topic><topic>Disease Models, Animal</topic><topic>Enzymes</topic><topic>Genomes</topic><topic>Group V Phospholipases A2 - genetics</topic><topic>Group V Phospholipases A2 - metabolism</topic><topic>Group X Phospholipases A2 - genetics</topic><topic>Group X Phospholipases A2 - metabolism</topic><topic>Immune response</topic><topic>Immune system</topic><topic>Immunohistochemistry</topic><topic>Immunopathogenesis</topic><topic>Impairment</topic><topic>Inflammation</topic><topic>Kinases</topic><topic>Lymphocytes T</topic><topic>Mammalian cells</topic><topic>Mammals</topic><topic>Medicine</topic><topic>Membranes</topic><topic>Mice</topic><topic>Mice, Knockout</topic><topic>Neutrophils</topic><topic>Ovalbumin</topic><topic>Ovalbumin - 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Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>PloS one</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Henderson, Jr, William R</au><au>Ye, Xin</au><au>Lai, Ying</au><au>Ni, Zhanglin</au><au>Bollinger, James G</au><au>Tien, Ying-Tzang</au><au>Chi, Emil Y</au><au>Gelb, Michael H</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Key role of group v secreted phospholipase A2 in Th2 cytokine and dendritic cell-driven airway hyperresponsiveness and remodeling</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2013-02-25</date><risdate>2013</risdate><volume>8</volume><issue>2</issue><spage>e56172</spage><epage>e56172</epage><pages>e56172-e56172</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>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.
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.
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.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>23451035</pmid><doi>10.1371/journal.pone.0056172</doi><oa>free_for_read</oa></addata></record> |
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| subjects | Acids Allergens Allergies Animals Antigens Asthma Asthma - enzymology Asthma - genetics Asthma - immunology Biology Biosynthesis CD4-Positive T-Lymphocytes - metabolism Cell activation Cytokines Dendritic cells Disease Models, Animal Enzymes Genomes Group V Phospholipases A2 - genetics Group V Phospholipases A2 - metabolism Group X Phospholipases A2 - genetics Group X Phospholipases A2 - metabolism Immune response Immune system Immunohistochemistry Immunopathogenesis Impairment Inflammation Kinases Lymphocytes T Mammalian cells Mammals Medicine Membranes Mice Mice, Knockout Neutrophils Ovalbumin Ovalbumin - immunology Phospholipase Phospholipase A2 Polymerase Chain Reaction Remodeling Respiratory tract Studies Th2 Cells - metabolism |
| title | Key role of group v secreted phospholipase A2 in Th2 cytokine and dendritic cell-driven airway hyperresponsiveness and remodeling |
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