Leishmania infantum lipophosphoglycan induced-Prostaglandin E2 production in association with PPAR-γ expression via activation of Toll like receptors-1 and 2

Scientific Reports
Jonilson Berlink LimaValéria Matos Borges

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 PGE2 induction. Intact LPG, but not its glycan and lipid moieties, induced a range of proinflammatory responses, including PGE2 and 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 PGE2 and cytokine production. Moreover, treatment with rosiglitazone, an agonist of peroxisome proliferator-activated receptor gamma (PPAR-γ), also modulated the release of PGE2 and 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 r...Continue Reading

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Citations

May 24, 2019·Journal of Leukocyte Biology·Filipe S Pereira-DutraPatrícia T Bozza
Sep 24, 2020·Memórias do Instituto Oswaldo Cruz·Camila A CardosoRodrigo P Soares
Apr 21, 2018·Frontiers in Microbiology·Milena Lázaro-SouzaValéria M Borges
Sep 7, 2018·Frontiers in Microbiology·Rodrigo A López-MuñozJuan D Maya
Jul 30, 2019·Frontiers in Cellular and Infection Microbiology·Tamara da Silva VieiraRodrigo Pedro Soares
Mar 7, 2021·Veterinary Sciences·Ehab Kotb Elmahallawy, Abdulsalam A M Alkhaldi
Jul 21, 2021·International Journal of Molecular Sciences·Génesis PalaciosEmma Carmelo

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Methods Mentioned

BETA
glucosylation
nuclear translocation
transfection
Assay
light microscopy

Software Mentioned

GraphPad
GraphPad Prism
Image

Related Concepts