PMID- 27630451
OWN - NLM
STAT- MEDLINE
DCOM- 20170605
LR  - 20181113
IS  - 1466-1861 (Electronic)
IS  - 0962-9351 (Print)
IS  - 0962-9351 (Linking)
VI  - 2016
DP  - 2016
TI  - TLR Signalling Pathways Diverge in Their Ability to Induce PGE2.
PG  - 5678046
LID - 10.1155/2016/5678046 [doi]
LID - 5678046
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-kappaB 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.
FAU - Salvi, Valentina
AU  - Salvi V
AUID- ORCID: 0000-0003-4802-1524
AD  - Department of Molecular and Translational Medicine, University of Brescia, 25123 
      Brescia, Italy.
FAU - Vaira, Xenia
AU  - Vaira X
AD  - Department of Molecular and Translational Medicine, University of Brescia, 25123 
      Brescia, Italy.
FAU - Gianello, Veronica
AU  - Gianello V
AD  - Department of Molecular and Translational Medicine, University of Brescia, 25123 
      Brescia, Italy.
FAU - Vermi, William
AU  - Vermi W
AD  - Department of Molecular and Translational Medicine, University of Brescia, 25123 
      Brescia, Italy.
FAU - Bugatti, Mattia
AU  - Bugatti M
AD  - Department of Molecular and Translational Medicine, University of Brescia, 25123 
      Brescia, Italy.
FAU - Sozzani, Silvano
AU  - Sozzani S
AD  - Department of Molecular and Translational Medicine, University of Brescia, 25123 
      Brescia, Italy; Humanitas Clinical and Research Center, 20089 Rozzano, Italy.
FAU - Bosisio, Daniela
AU  - Bosisio D
AUID- ORCID: 0000-0001-6276-5365
AD  - Department of Molecular and Translational Medicine, University of Brescia, 25123 
      Brescia, Italy.
LA  - eng
PT  - Journal Article
DEP - 20160818
PL  - United States
TA  - Mediators Inflamm
JT  - Mediators of inflammation
JID - 9209001
RN  - 0 (Imidazoles)
RN  - 0 (Interleukin-8)
RN  - 0 (Lipopolysaccharides)
RN  - 0 (Toll-Like Receptor 4)
RN  - 0 (Toll-Like Receptor 7)
RN  - 0 (Toll-Like Receptor 8)
RN  - K7Q1JQR04M (Dinoprostone)
RN  - V3DMU7PVXF (resiquimod)
SB  - IM
MH  - Blotting, Western
MH  - Cells, Cultured
MH  - Dendritic Cells/drug effects/*metabolism
MH  - Dinoprostone/*metabolism
MH  - Electrophoresis, Polyacrylamide Gel
MH  - Humans
MH  - Imidazoles/pharmacology
MH  - Immunohistochemistry
MH  - Interleukin-8/metabolism
MH  - Lipopolysaccharides/pharmacology
MH  - Real-Time Polymerase Chain Reaction
MH  - Toll-Like Receptor 4/*metabolism
MH  - Toll-Like Receptor 7/*metabolism
MH  - Toll-Like Receptor 8/*metabolism
PMC - PMC5007370
EDAT- 2016/09/16 06:00
MHDA- 2017/06/06 06:00
PMCR- 2016/08/18
CRDT- 2016/09/16 06:00
PHST- 2016/05/11 00:00 [received]
PHST- 2016/07/17 00:00 [accepted]
PHST- 2016/09/16 06:00 [entrez]
PHST- 2016/09/16 06:00 [pubmed]
PHST- 2017/06/06 06:00 [medline]
PHST- 2016/08/18 00:00 [pmc-release]
AID - 10.1155/2016/5678046 [doi]
PST - ppublish
SO  - Mediators Inflamm. 2016;2016:5678046. doi: 10.1155/2016/5678046. Epub 2016 Aug 
      18.