A snake venom group IIA PLA2 with immunomodulatory activity induces formation of lipid droplets containing 15-d-PGJ2 in macrophages

Abstract Crotoxin B (CB) is a catalytically active group IIA sPLA2 from Crotalus durissus terrificus snake venom. In contrast to most GIIA sPLA2s, CB exhibits anti-inflammatory effects, including the ability to inhibit leukocyte functions. Lipid droplets (LDs) are lipid-rich organelles associated wi...

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Autores principales:	Karina Cristina Giannotti, Elbio Leiguez, Ana Eduarda Zulim de Carvalho, Neide Galvão Nascimento, Márcio Hideki Matsubara, Consuelo Latorre Fortes-Dias, Vanessa Moreira, Catarina Teixeira
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/15bb05564a004211a7e70bfd4f9799f7
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spelling	oai:doaj.org-article:15bb05564a004211a7e70bfd4f9799f72021-12-02T12:32:44ZA snake venom group IIA PLA2 with immunomodulatory activity induces formation of lipid droplets containing 15-d-PGJ2 in macrophages10.1038/s41598-017-04498-82045-2322https://doaj.org/article/15bb05564a004211a7e70bfd4f9799f72017-06-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-04498-8https://doaj.org/toc/2045-2322Abstract Crotoxin B (CB) is a catalytically active group IIA sPLA2 from Crotalus durissus terrificus snake venom. In contrast to most GIIA sPLA2s, 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-PGJ2 (15-Deoxy-Delta-12,14-prostaglandin J2) production and involvement of LDs in 15-d-PGJ2 biosynthesis were also investigated. Stimulation of murine macrophages with CB induced increased number of LDs and release of 15-d-PGJ2. 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-PGJ2 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-PGJ2, a pro-resolving lipid mediator. Together, our data indicate that an immunomodulatory GIIA sPLA2 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.Karina Cristina GiannottiElbio LeiguezAna Eduarda Zulim de CarvalhoNeide Galvão NascimentoMárcio Hideki MatsubaraConsuelo Latorre Fortes-DiasVanessa MoreiraCatarina TeixeiraNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-15 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Karina Cristina Giannotti Elbio Leiguez Ana Eduarda Zulim de Carvalho Neide Galvão Nascimento Márcio Hideki Matsubara Consuelo Latorre Fortes-Dias Vanessa Moreira Catarina Teixeira A snake venom group IIA PLA2 with immunomodulatory activity induces formation of lipid droplets containing 15-d-PGJ2 in macrophages
description	Abstract Crotoxin B (CB) is a catalytically active group IIA sPLA2 from Crotalus durissus terrificus snake venom. In contrast to most GIIA sPLA2s, 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-PGJ2 (15-Deoxy-Delta-12,14-prostaglandin J2) production and involvement of LDs in 15-d-PGJ2 biosynthesis were also investigated. Stimulation of murine macrophages with CB induced increased number of LDs and release of 15-d-PGJ2. 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-PGJ2 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-PGJ2, a pro-resolving lipid mediator. Together, our data indicate that an immunomodulatory GIIA sPLA2 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.
format	article
author	Karina Cristina Giannotti Elbio Leiguez Ana Eduarda Zulim de Carvalho Neide Galvão Nascimento Márcio Hideki Matsubara Consuelo Latorre Fortes-Dias Vanessa Moreira Catarina Teixeira
author_facet	Karina Cristina Giannotti Elbio Leiguez Ana Eduarda Zulim de Carvalho Neide Galvão Nascimento Márcio Hideki Matsubara Consuelo Latorre Fortes-Dias Vanessa Moreira Catarina Teixeira
author_sort	Karina Cristina Giannotti
title	A snake venom group IIA PLA2 with immunomodulatory activity induces formation of lipid droplets containing 15-d-PGJ2 in macrophages
title_short	A snake venom group IIA PLA2 with immunomodulatory activity induces formation of lipid droplets containing 15-d-PGJ2 in macrophages
title_full	A snake venom group IIA PLA2 with immunomodulatory activity induces formation of lipid droplets containing 15-d-PGJ2 in macrophages
title_fullStr	A snake venom group IIA PLA2 with immunomodulatory activity induces formation of lipid droplets containing 15-d-PGJ2 in macrophages
title_full_unstemmed	A snake venom group IIA PLA2 with immunomodulatory activity induces formation of lipid droplets containing 15-d-PGJ2 in macrophages
title_sort	snake venom group iia pla2 with immunomodulatory activity induces formation of lipid droplets containing 15-d-pgj2 in macrophages
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/15bb05564a004211a7e70bfd4f9799f7
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A snake venom group IIA PLA2 with immunomodulatory activity induces formation of lipid droplets containing 15-d-PGJ2 in macrophages

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