TLR Signalling Pathways Diverge in Their Ability to Induce PGE2

Valentina Salvi, Xenia Vaira, Veronica Gianello, William Vermi, Mattia Bugatti, Silvano Sozzani, Daniela Bosisio

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

PGE2 is a lipid mediator abundantly produced in inflamed tissues that exerts relevant immunoregulatory functions. Dendritic cells (DCs) are key players in the onset and shaping of the inflammatory and immune responses and, as such, are well known PGE2 targets. By contrast, the precise role of human DCs in the production of PGE2 is poorly characterized. Here, we asked whether different ligands of Toll-like receptors (TLRs), a relevant family of pathogen-sensing receptors, could induce PGE2 in human DCs. The only active ligands were LPS (TLR4 ligand) and R848 (TLR7-8 ligand) although all TLRs, but TLR9, were expressed and functional. While investigating the molecular mechanisms hindering the release of PGE2, our experiments highlighted so far oversight differences in TLR signalling pathways in terms of MAPK and NF-B activation. In addition, we identified that the PGE2-limiting checkpoint downstream TLR3, TLR5, and TLR7 was a defect in COX2 induction, while TLR1/2 and TLR2/6 failed to mobilize arachidonic acid, the substrate for the COX2 enzyme. Finally, we demonstrated the in vivo expression of PGE2 by myeloid CD11c+ cells, documenting a role for DCs in the production of PGE2 in human inflamed tissues.

Original languageEnglish
Article number5678046
JournalMediators of Inflammation
Volume2016
DOIs
Publication statusPublished - 2016

Fingerprint

Toll-Like Receptors
Dinoprostone
Dendritic Cells
Ligands
resiquimod
Myeloid Cells
Arachidonic Acid
Lipids
Enzymes

ASJC Scopus subject areas

  • Immunology
  • Cell Biology

Cite this

Salvi, V., Vaira, X., Gianello, V., Vermi, W., Bugatti, M., Sozzani, S., & Bosisio, D. (2016). TLR Signalling Pathways Diverge in Their Ability to Induce PGE2. Mediators of Inflammation, 2016, [5678046]. https://doi.org/10.1155/2016/5678046

TLR Signalling Pathways Diverge in Their Ability to Induce PGE2. / Salvi, Valentina; Vaira, Xenia; Gianello, Veronica; Vermi, William; Bugatti, Mattia; Sozzani, Silvano; Bosisio, Daniela.

In: Mediators of Inflammation, Vol. 2016, 5678046, 2016.

Research output: Contribution to journalArticle

Salvi, V, Vaira, X, Gianello, V, Vermi, W, Bugatti, M, Sozzani, S & Bosisio, D 2016, 'TLR Signalling Pathways Diverge in Their Ability to Induce PGE2', Mediators of Inflammation, vol. 2016, 5678046. https://doi.org/10.1155/2016/5678046
Salvi, Valentina ; Vaira, Xenia ; Gianello, Veronica ; Vermi, William ; Bugatti, Mattia ; Sozzani, Silvano ; Bosisio, Daniela. / TLR Signalling Pathways Diverge in Their Ability to Induce PGE2. In: Mediators of Inflammation. 2016 ; Vol. 2016.
@article{d56029851d2c4096973ea1f3c2ac3a5f,
title = "TLR Signalling Pathways Diverge in Their Ability to Induce PGE2",
abstract = "PGE2 is a lipid mediator abundantly produced in inflamed tissues that exerts relevant immunoregulatory functions. Dendritic cells (DCs) are key players in the onset and shaping of the inflammatory and immune responses and, as such, are well known PGE2 targets. By contrast, the precise role of human DCs in the production of PGE2 is poorly characterized. Here, we asked whether different ligands of Toll-like receptors (TLRs), a relevant family of pathogen-sensing receptors, could induce PGE2 in human DCs. The only active ligands were LPS (TLR4 ligand) and R848 (TLR7-8 ligand) although all TLRs, but TLR9, were expressed and functional. While investigating the molecular mechanisms hindering the release of PGE2, our experiments highlighted so far oversight differences in TLR signalling pathways in terms of MAPK and NF-B activation. In addition, we identified that the PGE2-limiting checkpoint downstream TLR3, TLR5, and TLR7 was a defect in COX2 induction, while TLR1/2 and TLR2/6 failed to mobilize arachidonic acid, the substrate for the COX2 enzyme. Finally, we demonstrated the in vivo expression of PGE2 by myeloid CD11c+ cells, documenting a role for DCs in the production of PGE2 in human inflamed tissues.",
author = "Valentina Salvi and Xenia Vaira and Veronica Gianello and William Vermi and Mattia Bugatti and Silvano Sozzani and Daniela Bosisio",
year = "2016",
doi = "10.1155/2016/5678046",
language = "English",
volume = "2016",
journal = "Mediators of Inflammation",
issn = "0962-9351",
publisher = "Hindawi Publishing Corporation",

}

TY - JOUR

T1 - TLR Signalling Pathways Diverge in Their Ability to Induce PGE2

AU - Salvi, Valentina

AU - Vaira, Xenia

AU - Gianello, Veronica

AU - Vermi, William

AU - Bugatti, Mattia

AU - Sozzani, Silvano

AU - Bosisio, Daniela

PY - 2016

Y1 - 2016

N2 - PGE2 is a lipid mediator abundantly produced in inflamed tissues that exerts relevant immunoregulatory functions. Dendritic cells (DCs) are key players in the onset and shaping of the inflammatory and immune responses and, as such, are well known PGE2 targets. By contrast, the precise role of human DCs in the production of PGE2 is poorly characterized. Here, we asked whether different ligands of Toll-like receptors (TLRs), a relevant family of pathogen-sensing receptors, could induce PGE2 in human DCs. The only active ligands were LPS (TLR4 ligand) and R848 (TLR7-8 ligand) although all TLRs, but TLR9, were expressed and functional. While investigating the molecular mechanisms hindering the release of PGE2, our experiments highlighted so far oversight differences in TLR signalling pathways in terms of MAPK and NF-B activation. In addition, we identified that the PGE2-limiting checkpoint downstream TLR3, TLR5, and TLR7 was a defect in COX2 induction, while TLR1/2 and TLR2/6 failed to mobilize arachidonic acid, the substrate for the COX2 enzyme. Finally, we demonstrated the in vivo expression of PGE2 by myeloid CD11c+ cells, documenting a role for DCs in the production of PGE2 in human inflamed tissues.

AB - PGE2 is a lipid mediator abundantly produced in inflamed tissues that exerts relevant immunoregulatory functions. Dendritic cells (DCs) are key players in the onset and shaping of the inflammatory and immune responses and, as such, are well known PGE2 targets. By contrast, the precise role of human DCs in the production of PGE2 is poorly characterized. Here, we asked whether different ligands of Toll-like receptors (TLRs), a relevant family of pathogen-sensing receptors, could induce PGE2 in human DCs. The only active ligands were LPS (TLR4 ligand) and R848 (TLR7-8 ligand) although all TLRs, but TLR9, were expressed and functional. While investigating the molecular mechanisms hindering the release of PGE2, our experiments highlighted so far oversight differences in TLR signalling pathways in terms of MAPK and NF-B activation. In addition, we identified that the PGE2-limiting checkpoint downstream TLR3, TLR5, and TLR7 was a defect in COX2 induction, while TLR1/2 and TLR2/6 failed to mobilize arachidonic acid, the substrate for the COX2 enzyme. Finally, we demonstrated the in vivo expression of PGE2 by myeloid CD11c+ cells, documenting a role for DCs in the production of PGE2 in human inflamed tissues.

UR - http://www.scopus.com/inward/record.url?scp=84984846458&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84984846458&partnerID=8YFLogxK

U2 - 10.1155/2016/5678046

DO - 10.1155/2016/5678046

M3 - Article

AN - SCOPUS:84984846458

VL - 2016

JO - Mediators of Inflammation

JF - Mediators of Inflammation

SN - 0962-9351

M1 - 5678046

ER -