A snake venom group IIA PLA2 with immunomodulatory activity induces formation of lipid droplets containing 15-d-PGJ(2) in macrophages
Autor(a) principal: | |
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Data de Publicação: | 2017 |
Outros Autores: | , , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Institucional da UNIFESP |
Texto Completo: | http://dx.doi.org/10.1038/s41598-017-04498-8 https://repositorio.unifesp.br/handle/11600/53640 |
Resumo: | Crotoxin B (CB) is a catalytically active group IIA sPLA(2) from Crotalus durissus terrificus snake venom. In contrast to most GIIA sPLA(2)s, CB exhibits anti-inflammatory effects, including the ability to inhibit leukocyte functions. Lipid droplets (LDs) are lipid-rich organelles associated with inflammation and recognized as a site for the synthesis of inflammatory lipid mediators. Here, the ability of CB to induce formation of LDs and the mechanisms involved in this effect were investigated in isolated macrophages. The profile of CB-induced 15-d-PGJ(2) (15-Deoxy-Delta-12,14-prostaglandin J2) production and involvement of LDs in 15-d-PGJ(2) biosynthesis were also investigated. Stimulation of murine macrophages with CB induced increased number of LDs and release of 15-d-PGJ(2). LDs induced by CB were associated to PLIN2 recruitment and expression and required activation of PKC, PI3K, MEK1/2, JNK, iPLA2 and PLD. Both 15-d-PGJ(2) and COX-1 were found in CB-induced LDs indicating that LDs contribute to the inhibitory effects of CB by acting as platform for synthesis of 15-d-PGJ(2), a proresolving lipid mediator. Together, our data indicate that an immunomodulatory GIIA sPLA(2) can directly induce LD formation and production of a pro-resolving mediator in an inflammatory cell and afford new insights into the roles of LDs in resolution of inflammatory processes. |
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A snake venom group IIA PLA2 with immunomodulatory activity induces formation of lipid droplets containing 15-d-PGJ(2) in macrophagesCrotoxin B (CB) is a catalytically active group IIA sPLA(2) from Crotalus durissus terrificus snake venom. In contrast to most GIIA sPLA(2)s, CB exhibits anti-inflammatory effects, including the ability to inhibit leukocyte functions. Lipid droplets (LDs) are lipid-rich organelles associated with inflammation and recognized as a site for the synthesis of inflammatory lipid mediators. Here, the ability of CB to induce formation of LDs and the mechanisms involved in this effect were investigated in isolated macrophages. The profile of CB-induced 15-d-PGJ(2) (15-Deoxy-Delta-12,14-prostaglandin J2) production and involvement of LDs in 15-d-PGJ(2) biosynthesis were also investigated. Stimulation of murine macrophages with CB induced increased number of LDs and release of 15-d-PGJ(2). LDs induced by CB were associated to PLIN2 recruitment and expression and required activation of PKC, PI3K, MEK1/2, JNK, iPLA2 and PLD. Both 15-d-PGJ(2) and COX-1 were found in CB-induced LDs indicating that LDs contribute to the inhibitory effects of CB by acting as platform for synthesis of 15-d-PGJ(2), a proresolving lipid mediator. Together, our data indicate that an immunomodulatory GIIA sPLA(2) can directly induce LD formation and production of a pro-resolving mediator in an inflammatory cell and afford new insights into the roles of LDs in resolution of inflammatory processes.Butantan Inst, Pharmacol Lab, Sao Paulo, SP, BrazilEzequiel Dias Fdn, Mol Biol & Bioinformat Lab, Belo Horizonte, MG, BrazilUniv Fed Sao Paulo, Paulista Sch Med, Dept Pharmacol, BR-04044020 Sao Paulo, BrazilUniv Fed Sao Paulo, Paulista Sch Med, Dept Pharmacol, BR-04044020 Sao Paulo, BrazilWeb of ScienceFundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP)Instituto Nacional de Ciencia e Tecnologia em Toxinas (INCTTOX)CNPq-PQFAPESPFAPESP: 11/21341-5INCTTOX: 08/57898-0CNPq-PQ: 306920/2011-5FAPESP: 13/22610-5FAPESP: 15/247013Nature Publishing Group2020-06-26T16:30:35Z2020-06-26T16:30:35Z2017info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersion-application/pdfhttp://dx.doi.org/10.1038/s41598-017-04498-8Scientific Reports. London, v. 7, p. -, 2017.10.1038/s41598-017-04498-8WOS000403874900081.pdf2045-2322https://repositorio.unifesp.br/handle/11600/53640WOS:000403874900081engScientific ReportsLondoninfo:eu-repo/semantics/openAccessGiannotti, Karina CristinaLeiguez, ElbioZulim de Carvalho, Ana EduardaNascimento, Neide GalvaoMatsubara, Marcio HidekiFortes-Dias, Consuelo LatorreMoreira, Vanessa [UNIFESP]Teixeira, Catarinareponame:Repositório Institucional da UNIFESPinstname:Universidade Federal de São Paulo (UNIFESP)instacron:UNIFESP2024-08-11T01:42:50Zoai:repositorio.unifesp.br/:11600/53640Repositório InstitucionalPUBhttp://www.repositorio.unifesp.br/oai/requestbiblioteca.csp@unifesp.bropendoar:34652024-08-11T01:42:50Repositório Institucional da UNIFESP - Universidade Federal de São Paulo (UNIFESP)false |
dc.title.none.fl_str_mv |
A snake venom group IIA PLA2 with immunomodulatory activity induces formation of lipid droplets containing 15-d-PGJ(2) in macrophages |
title |
A snake venom group IIA PLA2 with immunomodulatory activity induces formation of lipid droplets containing 15-d-PGJ(2) in macrophages |
spellingShingle |
A snake venom group IIA PLA2 with immunomodulatory activity induces formation of lipid droplets containing 15-d-PGJ(2) in macrophages Giannotti, Karina Cristina |
title_short |
A snake venom group IIA PLA2 with immunomodulatory activity induces formation of lipid droplets containing 15-d-PGJ(2) in macrophages |
title_full |
A snake venom group IIA PLA2 with immunomodulatory activity induces formation of lipid droplets containing 15-d-PGJ(2) in macrophages |
title_fullStr |
A snake venom group IIA PLA2 with immunomodulatory activity induces formation of lipid droplets containing 15-d-PGJ(2) in macrophages |
title_full_unstemmed |
A snake venom group IIA PLA2 with immunomodulatory activity induces formation of lipid droplets containing 15-d-PGJ(2) in macrophages |
title_sort |
A snake venom group IIA PLA2 with immunomodulatory activity induces formation of lipid droplets containing 15-d-PGJ(2) in macrophages |
author |
Giannotti, Karina Cristina |
author_facet |
Giannotti, Karina Cristina Leiguez, Elbio Zulim de Carvalho, Ana Eduarda Nascimento, Neide Galvao Matsubara, Marcio Hideki Fortes-Dias, Consuelo Latorre Moreira, Vanessa [UNIFESP] Teixeira, Catarina |
author_role |
author |
author2 |
Leiguez, Elbio Zulim de Carvalho, Ana Eduarda Nascimento, Neide Galvao Matsubara, Marcio Hideki Fortes-Dias, Consuelo Latorre Moreira, Vanessa [UNIFESP] Teixeira, Catarina |
author2_role |
author author author author author author author |
dc.contributor.author.fl_str_mv |
Giannotti, Karina Cristina Leiguez, Elbio Zulim de Carvalho, Ana Eduarda Nascimento, Neide Galvao Matsubara, Marcio Hideki Fortes-Dias, Consuelo Latorre Moreira, Vanessa [UNIFESP] Teixeira, Catarina |
description |
Crotoxin B (CB) is a catalytically active group IIA sPLA(2) from Crotalus durissus terrificus snake venom. In contrast to most GIIA sPLA(2)s, CB exhibits anti-inflammatory effects, including the ability to inhibit leukocyte functions. Lipid droplets (LDs) are lipid-rich organelles associated with inflammation and recognized as a site for the synthesis of inflammatory lipid mediators. Here, the ability of CB to induce formation of LDs and the mechanisms involved in this effect were investigated in isolated macrophages. The profile of CB-induced 15-d-PGJ(2) (15-Deoxy-Delta-12,14-prostaglandin J2) production and involvement of LDs in 15-d-PGJ(2) biosynthesis were also investigated. Stimulation of murine macrophages with CB induced increased number of LDs and release of 15-d-PGJ(2). LDs induced by CB were associated to PLIN2 recruitment and expression and required activation of PKC, PI3K, MEK1/2, JNK, iPLA2 and PLD. Both 15-d-PGJ(2) and COX-1 were found in CB-induced LDs indicating that LDs contribute to the inhibitory effects of CB by acting as platform for synthesis of 15-d-PGJ(2), a proresolving lipid mediator. Together, our data indicate that an immunomodulatory GIIA sPLA(2) can directly induce LD formation and production of a pro-resolving mediator in an inflammatory cell and afford new insights into the roles of LDs in resolution of inflammatory processes. |
publishDate |
2017 |
dc.date.none.fl_str_mv |
2017 2020-06-26T16:30:35Z 2020-06-26T16:30:35Z |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
format |
article |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
http://dx.doi.org/10.1038/s41598-017-04498-8 Scientific Reports. London, v. 7, p. -, 2017. 10.1038/s41598-017-04498-8 WOS000403874900081.pdf 2045-2322 https://repositorio.unifesp.br/handle/11600/53640 WOS:000403874900081 |
url |
http://dx.doi.org/10.1038/s41598-017-04498-8 https://repositorio.unifesp.br/handle/11600/53640 |
identifier_str_mv |
Scientific Reports. London, v. 7, p. -, 2017. 10.1038/s41598-017-04498-8 WOS000403874900081.pdf 2045-2322 WOS:000403874900081 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
Scientific Reports |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
- application/pdf |
dc.coverage.none.fl_str_mv |
London |
dc.publisher.none.fl_str_mv |
Nature Publishing Group |
publisher.none.fl_str_mv |
Nature Publishing Group |
dc.source.none.fl_str_mv |
reponame:Repositório Institucional da UNIFESP instname:Universidade Federal de São Paulo (UNIFESP) instacron:UNIFESP |
instname_str |
Universidade Federal de São Paulo (UNIFESP) |
instacron_str |
UNIFESP |
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UNIFESP |
reponame_str |
Repositório Institucional da UNIFESP |
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Repositório Institucional da UNIFESP |
repository.name.fl_str_mv |
Repositório Institucional da UNIFESP - Universidade Federal de São Paulo (UNIFESP) |
repository.mail.fl_str_mv |
biblioteca.csp@unifesp.br |
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