Activation of PAF-receptor induces regulatory dendritic cells through PGE2 and IL-10

Koga, Marianna M.; Bizzarro, Bruna; Sá-Nunes, Anderson; Ríos, Francisco; Jancar, Sônia

doi:10.1016/j.plefa.2013.09.003

Cited by 28 publications

(25 citation statements)

References 30 publications

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“…However, when DCs were pre-treated with the COX-2 non-selective inhibitor indomethacin (15 µM) or the selective inhibitor nimesulide (10 µM), no effects were observed in IL-10 levels; hence, the IL-10 production was not affected by endogenous PGE 2 , since PGE 2 was completely suppressed by COX inhibitors. The blockage of PAFR with WEB2086 reduced both PGE 2 and IL-10 LPS-induced production (Figure 2A), thus confirming our previous data [8].The requirement of CREB activation for IL-10 production was also excluded, since no changes in the IL-10 production were observed in LPS stimulated DCs in the presence of the CREB inhibitor KG-501 (10 µM) ( Figure 2B). Additionally, DCs pre-treatment with the PAFR antagonist WEB2086 (WEB-50 µM) did not affect CREB phosphorylation ( Figure 2C).…”

Section: Pafr Ligands Are Produced By Lps-stimulated Dcssupporting

confidence: 88%

“…Prostaglandin E2 (PGE 2 ), a lipid mediator rapidly synthesized by the inducible cyclooxygenase (COX-2) upon LPS stimulus, was also downregulated by the blockage of PAFR. Moreover, when DCs were treated with selective COX-2 inhibitors PGE 2 production was abrogated, their ability to promote T cell proliferation was increased to the same levels observed in the presence of PAFR antagonists, but no effects were observed in IL-10 production [8]. These data indicated that IL-10 and PGE 2 induction partially occurred via PAFR activation but they also suggested the existence of another LPS-induced IL-10…”

Section: Introductionmentioning

confidence: 78%

“…In previous studies, we described the effect of the PAFR blockage in DCs during maturation induced by LPS. A pretreatment with a PAFR antagonist reduced the IL-10 and PGE 2 secretion by DCs and increased their ability in promoting T cell proliferation and Th1-like adaptive response in vitro and in vivo [6,8].…”

Section: Discussionmentioning

confidence: 99%

“…In response, transcription factors such as CREB (the cAMP response element binding protein) bind to the Il10 promoter to induce IL-10 production. We have previously shown that PAFR activation contributes to the production of both PGE 2 and IL-10 in LPS-stimulated DCs [8]. However, when DCs were pre-treated with the COX-2 non-selective inhibitor indomethacin (15 µM) or the selective inhibitor nimesulide (10 µM), no effects were observed in IL-10 levels; hence, the IL-10 production was not affected by endogenous PGE 2 , since PGE 2 was completely suppressed by COX inhibitors.…”

Section: Pafr Ligands Are Produced By Lps-stimulated Dcsmentioning

confidence: 99%

“…LPS induces IL-10 production through PAFR and independent of COX-2/PGE 2 axis LPS has been reported to induce PGE 2 synthesis through COX-2 in DCs [8,13,14]. The secreted PGE 2 could then act on its receptors EP2 and EP4 expressed on the cell membrane and increases the levels of cyclic adenosine monophosphate (cAMP) cellular [15].…”

Section: Pafr Ligands Are Produced By Lps-stimulated Dcsmentioning

confidence: 99%

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Platelet-Activation Factor Receptor Induces Interleukin 10 Production through STAT3 Activation in Dendritic Cells

Koga¹,

Filgueiras²,

Jancar³

2017

J immuno Biol

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The activation of the platelet-activating factor receptor (PAFR) is associated to a suppressor phenotype in macrophages and dendritic cells (DCs). In the present study, we investigated mechanisms underlying the production of the interleukin 10 (IL-10) through PAFR activation in murine DCs. For this purpose, BALB/c mice bone marrowderived DCs were differentiated by GM-CSF treatment and stimulated with LPS in the presence of the PAFR antagonist WEB2086. Signalling pathways downstream to TLR4 activation were investigated. We found that LPS stimulus induced PAFR ligands generation by DCs, but it did not affect the PAFR expression. The LPS-induced IL-10 production was found to be partially dependent of PAFR, since it was reduced in the presence of WEB2086. The IL-10 production through PAFR activation was independent on CREB and PPARγ, as the treatment with selective inhibitors of these pathways did not affect the IL-10 production. TLR4 adaptor molecules (MyD88 and TRIF) expression, MAPK, or NF-κB (p105/50 and p65 subunits) activation pathways were also excluded, since they were not affected by the treatment with WEB2086. The blockage of PAFR by WEB2086 downregulated the STAT3 (Tyr705) phosphorylation induced by LPS. Additionally, DCs treated with STAT3 inhibitor (S3I-201) showed reduced IL-10 production to the same levels observed in DCs treated with WEB2086. The requirement of STAT3 was confirmed in PAFR-KO DCs, since the STAT3 inhibition did not affect IL-10 production by these cells. Our data show an additional molecular mechanism whereby PAFR contributes to IL-10 production in DCs and support the importance of the PAFR activation in DCs phenotype and function.

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Section: Pafr Ligands Are Produced By Lps-stimulated Dcssupporting

confidence: 88%

Section: Introductionmentioning

confidence: 78%

Section: Discussionmentioning

confidence: 99%

Section: Pafr Ligands Are Produced By Lps-stimulated Dcsmentioning

confidence: 99%

Section: Pafr Ligands Are Produced By Lps-stimulated Dcsmentioning

confidence: 99%

See 3 more Smart Citations

Platelet-Activation Factor Receptor Induces Interleukin 10 Production through STAT3 Activation in Dendritic Cells

Koga¹,

Filgueiras²,

Jancar³

2017

J immuno Biol

Self Cite

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Progress in the Development of Platelet‐Activating Factor Receptor (PAFr) Antagonists and Applications in the Treatment of Inflammatory Diseases

et al. 2018

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Platelet-activating factor (PAF) and its receptor (PAFr) have been implicated in a wide range of diseases and disorders that originate from the activation of inflammatory pathways. Although the exact structure of the binding site on the PAFr remains unknown, the PAFr is a well-established therapeutic target, and an array of structurally diverse PAFr antagonists have been identified. These include compounds that are structurally similar to the natural PAF ligand, synthetic heterocycles, complex polycyclic natural products, and various metal complexes. This review provides an update on more than 20 years of progress in this area. The development and synthesis of new PAFr antagonists, structure-activity relationship studies, the biological activity of these molecules, and their therapeutic potential are discussed.

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Cancer Therapy-Induced Inflammation and Its Consequences

Saito

Rangel

Chandler

et al. 2023

Interdisciplinary Biotechnological Advances

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Activation of PAF-receptor induces regulatory dendritic cells through PGE2 and IL-10

Cited by 28 publications

References 30 publications

Platelet-Activation Factor Receptor Induces Interleukin 10 Production through STAT3 Activation in Dendritic Cells

Platelet-Activation Factor Receptor Induces Interleukin 10 Production through STAT3 Activation in Dendritic Cells

Progress in the Development of Platelet‐Activating Factor Receptor (PAFr) Antagonists and Applications in the Treatment of Inflammatory Diseases

Cancer Therapy-Induced Inflammation and Its Consequences

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