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

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dc.citation.volume7]
dc.contributor.authorGiannotti, Karina Cristina
dc.contributor.authorLeiguez, Elbio
dc.contributor.authorZulim de Carvalho, Ana Eduarda
dc.contributor.authorNascimento, Neide Galvao
dc.contributor.authorMatsubara, Marcio Hideki
dc.contributor.authorFortes-Dias, Consuelo Latorre
dc.contributor.authorMoreira, Vanessa [UNIFESP]
dc.contributor.authorTeixeira, Catarina
dc.coverageLondon
dc.date.accessioned2020-06-26T16:30:35Z
dc.date.available2020-06-26T16:30:35Z
dc.date.issued2017
dc.description.abstractCrotoxin 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.en
dc.description.affiliationButantan Inst, Pharmacol Lab, Sao Paulo, SP, Brazil
dc.description.affiliationEzequiel Dias Fdn, Mol Biol & Bioinformat Lab, Belo Horizonte, MG, Brazil
dc.description.affiliationUniv Fed Sao Paulo, Paulista Sch Med, Dept Pharmacol, BR-04044020 Sao Paulo, Brazil
dc.description.affiliationUnifespUniv Fed Sao Paulo, Paulista Sch Med, Dept Pharmacol, BR-04044020 Sao Paulo, Brazil
dc.description.sourceWeb of Science
dc.description.sponsorshipFundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP)
dc.description.sponsorshipInstituto Nacional de Ciencia e Tecnologia em Toxinas (INCTTOX)
dc.description.sponsorshipCNPq-PQ
dc.description.sponsorshipFAPESP
dc.description.sponsorshipIDFAPESP: 11/21341-5
dc.description.sponsorshipIDINCTTOX: 08/57898-0
dc.description.sponsorshipIDCNPq-PQ: 306920/2011-5
dc.description.sponsorshipIDFAPESP: 13/22610-5
dc.description.sponsorshipIDFAPESP: 15/247013
dc.format.extent-
dc.identifierhttp://dx.doi.org/10.1038/s41598-017-04498-8]
dc.identifier.citationScientific Reports. London, v. 7, p. -, 2017.
dc.identifier.doi10.1038/s41598-017-04498-8
dc.identifier.fileWOS000403874900081.pdf
dc.identifier.issn2045-2322
dc.identifier.urihttps://repositorio.unifesp.br/handle/11600/53640
dc.identifier.wosWOS:000403874900081
dc.language.isoeng
dc.publisherNature Publishing Group
dc.relation.ispartofScientific Reports
dc.rightsinfo:eu-repo/semantics/openAccess
dc.titleA snake venom group IIA PLA2 with immunomodulatory activity induces formation of lipid droplets containing 15-d-PGJ(2) in macrophagesen
dc.typeinfo:eu-repo/semantics/article
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