A snake venom group IIA PLA2 with immunomodulatory activity induces formation of lipid droplets containing 15-d-PGJ(2) in macrophages

Detalhes bibliográficos
Autor(a) principal: Giannotti, Karina Cristina
Data de Publicação: 2017
Outros Autores: Leiguez, Elbio, Zulim de Carvalho, Ana Eduarda, Nascimento, Neide Galvao, Matsubara, Marcio Hideki, Fortes-Dias, Consuelo Latorre, Moreira, Vanessa [UNIFESP], Teixeira, Catarina
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.
id UFSP_4a54a2a34cca30af7a73614cd61056a6
oai_identifier_str oai:repositorio.unifesp.br/:11600/53640
network_acronym_str UFSP
network_name_str Repositório Institucional da UNIFESP
repository_id_str 3465
spelling 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
institution UNIFESP
reponame_str Repositório Institucional da UNIFESP
collection 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
_version_ 1814268448315801600