Leishmania infantum lipophosphoglycan induced-Prostaglandin E2production in association with PPAR-γ expression via activation of Toll like receptors-1 and 2

Fundação Oswaldo Cruz. Instituto Gonçalo Muniz. Salvador, BA, Brasil / Universidade Federal do Oeste da Bahia. Centro de Ciências Biológicas e da Saúde. Barreiras, BA, Brasil.
Fundação Oswaldo Cruz. Instituto Gonçalo Muniz. Salvador, BA, Brasil / Universidade Federal do Oeste da Bahia. Centro de Ciências Biológicas e da Saúde. Barreiras, BA, Brasil.
Fundação Oswaldo Cruz. Instituto Gonçalo Muniz. Salvador, BA, Brasil / Universidade Federal da Bahia. Salvador, BA, Brasil.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Imunofarmacologia. Rio de Janeiro, RJ. Brasil.
Fundação Oswaldo Cruz. Instituto René Rachou. Belo Horizonte, MG, Brasil
Fundação Oswaldo Cruz. Instituto Gonçalo Muniz. Salvador, BA, Brasil / Universidade Federal da Bahia. Salvador, BA, Brasil.
Fundação Oswaldo Cruz. Instituto René Rachou. Belo Horizonte, MG, Brasil.
Fundação Oswaldo Cruz. Instituto Gonçalo Muniz. Salvador, BA, Brasil / Universidade Federal da Bahia. Salvador, BA, Brasil.
Universidade Federal do Rio de Janeiro. NUPEM. Campus Macaé. macaé, RJ, Brasil.
Institut National de la Recherche Scientifique. Institut Armand-Frappier. Laval, Canada.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Imunofarmacologia. Rio de Janeiro, RJ. Brasil.
Fundação Oswaldo Cruz. Instituto René Rachou. Belo Horizonte, MG, Brasil
Fundação Oswaldo Cruz. Instituto Gonçalo Muniz. Salvador, BA, Brasil / Universidade Federal da Bahia. Salvador, BA, Brasil.

Abstract

Lipophosphoglycan (LPG) is a key virulence factor expressed on the surfaces of Leishmania promastigotes. Although LPG is known to activate macrophages, the underlying mechanisms resulting in the production of prostaglandin E2(PGE2) via signaling pathways remain unknown. Here, the inflammatory response arising from stimulation by Leishmania infantum LPG and/or its lipid and glycan motifs was evaluated with regard to PGE2induction. Intact LPG, but not its glycan and lipid moieties, induced a range of proinflammatory responses, including PGE2and nitric oxide (NO) release, increased lipid droplet formation, and iNOS and COX2 expression. LPG also induced ERK-1/2 and JNK phosphorylation in macrophages, in addition to the release of PGE2, MCP-1, IL-6, TNF-α and IL-12p70, but not IL-10. Pharmacological inhibition of ERK1/2 and PKC affected PGE2and cytokine production. Moreover, treatment with rosiglitazone, an agonist of peroxisome proliferator-activated receptor gamma (PPAR-γ), also modulated the release of PGE2and other proinflammatory mediators. Finally, we determined that LPG-induced PPAR-γ signaling occurred via TLR1/2. Taken together, these results reinforce the role played by L. infantum-derived LPG in the proinflammatory response seen in Leishmania infection.

Keywords in Portuguese

Leishmania infantum
PPRA
Prostaglandina
Receptores Toll-Like
Glicoproteínas de Membrana Associadas ao Lisossomo

Keywords

Leishmania infantum
PPRA-y expression
Prostaglandin E2
Toll like receptors-1 and 2
Lipophosphoglycan

Publisher

Nature Publishing Group

Citation

LIMA, Jonilson Berlink; et al. Leishmania infantum lipophosphoglycan induced- Prostaglandin E2 production in association with PPAR-γ expression via activation of Toll like receptors-1 and 2. Scientifc Reports, v.7: 14321, 11p, Oct. 2017.

DOI

10.1038/s41598-017-14229-8

ISSN

2045-2322

Please use this identifier to cite or link to this item: https://www.arca.fiocruz.br/handle/icict/24884

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Open access

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