Leishmania infantum lipophosphoglycan induced-Prostaglandin E2 production in association with PPAR-γ expression via activation of Toll like receptors-1 and 2. Issue 1 (December 2017)

• Record Type: Journal Article
• Authors: Lima, Jonilson; Araújo-Santos, Théo; Lázaro-Souza, Milena; Carneiro, Alan; Ibraim, Izabela; Jesus-Santos, Flávio; Luz, Nívea; Pontes, Sara; Entringer, Petter; Descoteaux, Albert; Bozza, Patrícia; Soares, Rodrigo; Borges, Valéria
• Is Part Of: Scientific reports. Volume 7:Issue 1(2017)
• Page Start: 1
• Page End: 11
• Publication Date: 2017-12
• Subjects: Natural history -- Research -- Periodicals; Biology -- Research -- Periodicals; Physical sciences -- Research -- Periodicals; Earth sciences -- Research -- Periodicals; Environmental sciences -- Research -- Periodicals; 502.85
• DOI: 10.1038/s41598-017-14229-8
• Languages: English
• ISSNs: 2045-2322

Abstract

Abstract Lipophosphoglycan (LPG) is a key virulence factor expressed on the surfaces ofLeishmania 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 byLeishmania 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 byL .infantum- derived LPG in the proinflammatory response seen inLeishmania infection.