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Administration of reconstituted polyphenol oil bodies efficiently suppresses dendritic cell inflammatory pathways and acute intestinal inflammation.

Cavalcanti E, Vadrucci E, Delvecchio FR, Addabbo F, Bettini S, Liou R, Monsurrò V, Huang AY, Pizarro TT, Santino A, Chieppa M - PLoS ONE (2014)

Bottom Line: The in vitro suppressive properties of several polyphenols were first tested and compared for dendritic cells (DCs) production of inflammatory cytokines.Our results showed that administration of low dose reconstituted polyphenol OBs inhibited LPS-mediated inflammatory cytokine secretion, including IL-6, IL-23, and IL-12, while increasing IL-10 and IL-1Rα production.Mice treated with the polyphenol-containing reconstituted OBs (ROBs) were partially protected from dextran sodium sulfate (DSS)-induced colitis and associated weight loss, while mortality and inflammatory scores revealed an overall anti-inflammatory effect that was likely mediated by impaired DC immune responses.

View Article: PubMed Central - PubMed

Affiliation: Laboratory of Experimental Immunopathology, IRCCS "de Bellis," Castellana Grotte (BA), Italy.

ABSTRACT
Polyphenols are natural compounds capable of interfering with the inflammatory pathways of several in vitro model systems. In this study, we developed a stable and effective strategy to administer polyphenols to treat in vivo models of acute intestinal inflammation. The in vitro suppressive properties of several polyphenols were first tested and compared for dendritic cells (DCs) production of inflammatory cytokines. A combination of the polyphenols, quercetin and piperine, were then encapsulated into reconstituted oil bodies (OBs) in order to increase their stability. Our results showed that administration of low dose reconstituted polyphenol OBs inhibited LPS-mediated inflammatory cytokine secretion, including IL-6, IL-23, and IL-12, while increasing IL-10 and IL-1Rα production. Mice treated with the polyphenol-containing reconstituted OBs (ROBs) were partially protected from dextran sodium sulfate (DSS)-induced colitis and associated weight loss, while mortality and inflammatory scores revealed an overall anti-inflammatory effect that was likely mediated by impaired DC immune responses. Our study indicates that the administration of reconstituted quercetin and piperine-containing OBs may represent an effective and potent anti-inflammatory strategy to treat acute intestinal inflammation.

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Related in: MedlinePlus

Modulated activation of pro-inflammatory MAPK p38 signaling and inducible COX-2 on ROBs-QP treated DCs.DCs were cultured in the presence of either ROBs-P, ROBs-Q or ROBs-QP as mentioned previously; empty ROBs were used as control. LPS (A) or PG (B) was administered at indicated time points. DC lysates were subjected to immunoblotting with antibodies to detect total and phosphorylated forms of p38 MAPK and COX-2. Representative immunoblots from at least three independent experiments are shown for each condition. Each bar represents the mean ± SEM of densitometric analyses for phosphorylated proteins normalized to their respective total forms; *P<0.05, **P<0.01 vs. basal conditions.
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pone-0088898-g004: Modulated activation of pro-inflammatory MAPK p38 signaling and inducible COX-2 on ROBs-QP treated DCs.DCs were cultured in the presence of either ROBs-P, ROBs-Q or ROBs-QP as mentioned previously; empty ROBs were used as control. LPS (A) or PG (B) was administered at indicated time points. DC lysates were subjected to immunoblotting with antibodies to detect total and phosphorylated forms of p38 MAPK and COX-2. Representative immunoblots from at least three independent experiments are shown for each condition. Each bar represents the mean ± SEM of densitometric analyses for phosphorylated proteins normalized to their respective total forms; *P<0.05, **P<0.01 vs. basal conditions.

Mentions: As shown in Figure 4A and B, BMDCs exposed to either LPS or PG acutely activated the MAPK p38 signaling pathway. Treated cells significantly increased levels of p38 MAPK phosphorylation as compared to basal levels. Time course experiments (Baseline, 10′, 30′, 120′) indicated both TLR4- and TLR2-dependent activation of p38 MAPK peaks during the first 10 min and remained sustained for 2 h. Quantitative analysis of phosphorylation levels also revealed a different order of magnitude for LPS- and PG-mediated phosphorylation of p38 MAPK (Fig. 4A and B).


Administration of reconstituted polyphenol oil bodies efficiently suppresses dendritic cell inflammatory pathways and acute intestinal inflammation.

Cavalcanti E, Vadrucci E, Delvecchio FR, Addabbo F, Bettini S, Liou R, Monsurrò V, Huang AY, Pizarro TT, Santino A, Chieppa M - PLoS ONE (2014)

Modulated activation of pro-inflammatory MAPK p38 signaling and inducible COX-2 on ROBs-QP treated DCs.DCs were cultured in the presence of either ROBs-P, ROBs-Q or ROBs-QP as mentioned previously; empty ROBs were used as control. LPS (A) or PG (B) was administered at indicated time points. DC lysates were subjected to immunoblotting with antibodies to detect total and phosphorylated forms of p38 MAPK and COX-2. Representative immunoblots from at least three independent experiments are shown for each condition. Each bar represents the mean ± SEM of densitometric analyses for phosphorylated proteins normalized to their respective total forms; *P<0.05, **P<0.01 vs. basal conditions.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3928302&req=5

pone-0088898-g004: Modulated activation of pro-inflammatory MAPK p38 signaling and inducible COX-2 on ROBs-QP treated DCs.DCs were cultured in the presence of either ROBs-P, ROBs-Q or ROBs-QP as mentioned previously; empty ROBs were used as control. LPS (A) or PG (B) was administered at indicated time points. DC lysates were subjected to immunoblotting with antibodies to detect total and phosphorylated forms of p38 MAPK and COX-2. Representative immunoblots from at least three independent experiments are shown for each condition. Each bar represents the mean ± SEM of densitometric analyses for phosphorylated proteins normalized to their respective total forms; *P<0.05, **P<0.01 vs. basal conditions.
Mentions: As shown in Figure 4A and B, BMDCs exposed to either LPS or PG acutely activated the MAPK p38 signaling pathway. Treated cells significantly increased levels of p38 MAPK phosphorylation as compared to basal levels. Time course experiments (Baseline, 10′, 30′, 120′) indicated both TLR4- and TLR2-dependent activation of p38 MAPK peaks during the first 10 min and remained sustained for 2 h. Quantitative analysis of phosphorylation levels also revealed a different order of magnitude for LPS- and PG-mediated phosphorylation of p38 MAPK (Fig. 4A and B).

Bottom Line: The in vitro suppressive properties of several polyphenols were first tested and compared for dendritic cells (DCs) production of inflammatory cytokines.Our results showed that administration of low dose reconstituted polyphenol OBs inhibited LPS-mediated inflammatory cytokine secretion, including IL-6, IL-23, and IL-12, while increasing IL-10 and IL-1Rα production.Mice treated with the polyphenol-containing reconstituted OBs (ROBs) were partially protected from dextran sodium sulfate (DSS)-induced colitis and associated weight loss, while mortality and inflammatory scores revealed an overall anti-inflammatory effect that was likely mediated by impaired DC immune responses.

View Article: PubMed Central - PubMed

Affiliation: Laboratory of Experimental Immunopathology, IRCCS "de Bellis," Castellana Grotte (BA), Italy.

ABSTRACT
Polyphenols are natural compounds capable of interfering with the inflammatory pathways of several in vitro model systems. In this study, we developed a stable and effective strategy to administer polyphenols to treat in vivo models of acute intestinal inflammation. The in vitro suppressive properties of several polyphenols were first tested and compared for dendritic cells (DCs) production of inflammatory cytokines. A combination of the polyphenols, quercetin and piperine, were then encapsulated into reconstituted oil bodies (OBs) in order to increase their stability. Our results showed that administration of low dose reconstituted polyphenol OBs inhibited LPS-mediated inflammatory cytokine secretion, including IL-6, IL-23, and IL-12, while increasing IL-10 and IL-1Rα production. Mice treated with the polyphenol-containing reconstituted OBs (ROBs) were partially protected from dextran sodium sulfate (DSS)-induced colitis and associated weight loss, while mortality and inflammatory scores revealed an overall anti-inflammatory effect that was likely mediated by impaired DC immune responses. Our study indicates that the administration of reconstituted quercetin and piperine-containing OBs may represent an effective and potent anti-inflammatory strategy to treat acute intestinal inflammation.

Show MeSH
Related in: MedlinePlus