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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

ROBs-QP administration promotes a unique cytokine profile in LPS-treated DCs.BMDCs were exposed to different ROBs-QP concentrations on day 5 and 7. LPS [1 µg/ml] was administered on day 8, and 24 h later SNs were collected. Cytokine protein levels were measured by ELISA. Data are shown as mean ± S.D. of five independent experiments. Statistically significant differences were considered when **P<0.01; ***P<0.001 between control (LPS, no polyphenols) and LPS-ROBS-QP-treated cells.
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pone-0088898-g005: ROBs-QP administration promotes a unique cytokine profile in LPS-treated DCs.BMDCs were exposed to different ROBs-QP concentrations on day 5 and 7. LPS [1 µg/ml] was administered on day 8, and 24 h later SNs were collected. Cytokine protein levels were measured by ELISA. Data are shown as mean ± S.D. of five independent experiments. Statistically significant differences were considered when **P<0.01; ***P<0.001 between control (LPS, no polyphenols) and LPS-ROBS-QP-treated cells.

Mentions: Most of the in vivo studies following polyphenol administration failed translation into clinical practice due to rapid polyphenol degradation in water and the high dosage required to obtain significant results. DCs were treated as previously described using different doses of ROBs–QP, and production of several DC-derived cytokines was evaluated. Figure 5 shows that ROBs-QP effectively inhibits the production of acute phase inflammatory cytokines, including TNFα, IL-6, IL-23 and IL-12. Administration of 100 µM of ROBs-QP reduced DC activity, as demonstrated by decreased cytokine production, and 50 µM ROBs-QP revealed low toxicity as viability was comparable among treated and untreated DCs. Administration of 50 µM ROBs-QP decreased TNFα, IL-12 IL-23, IL-6, CCL3, CXCL1 and even IL-10 production. IL-1Rα, IL-1β, CCL5 and TGFβ secretion was not affected. Administration of 25–12.5 µM ROBs-QP still had the ability to inhibit the acute inflammatory pathway and to induce increased levels of anti-inflammatory cytokines. Efficacy of ROBs-QP was lost at 6.25 µM, with the exception of IL-6 production that was still potently inhibited.


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)

ROBs-QP administration promotes a unique cytokine profile in LPS-treated DCs.BMDCs were exposed to different ROBs-QP concentrations on day 5 and 7. LPS [1 µg/ml] was administered on day 8, and 24 h later SNs were collected. Cytokine protein levels were measured by ELISA. Data are shown as mean ± S.D. of five independent experiments. Statistically significant differences were considered when **P<0.01; ***P<0.001 between control (LPS, no polyphenols) and LPS-ROBS-QP-treated cells.
© Copyright Policy
Related In: Results  -  Collection

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

pone-0088898-g005: ROBs-QP administration promotes a unique cytokine profile in LPS-treated DCs.BMDCs were exposed to different ROBs-QP concentrations on day 5 and 7. LPS [1 µg/ml] was administered on day 8, and 24 h later SNs were collected. Cytokine protein levels were measured by ELISA. Data are shown as mean ± S.D. of five independent experiments. Statistically significant differences were considered when **P<0.01; ***P<0.001 between control (LPS, no polyphenols) and LPS-ROBS-QP-treated cells.
Mentions: Most of the in vivo studies following polyphenol administration failed translation into clinical practice due to rapid polyphenol degradation in water and the high dosage required to obtain significant results. DCs were treated as previously described using different doses of ROBs–QP, and production of several DC-derived cytokines was evaluated. Figure 5 shows that ROBs-QP effectively inhibits the production of acute phase inflammatory cytokines, including TNFα, IL-6, IL-23 and IL-12. Administration of 100 µM of ROBs-QP reduced DC activity, as demonstrated by decreased cytokine production, and 50 µM ROBs-QP revealed low toxicity as viability was comparable among treated and untreated DCs. Administration of 50 µM ROBs-QP decreased TNFα, IL-12 IL-23, IL-6, CCL3, CXCL1 and even IL-10 production. IL-1Rα, IL-1β, CCL5 and TGFβ secretion was not affected. Administration of 25–12.5 µM ROBs-QP still had the ability to inhibit the acute inflammatory pathway and to induce increased levels of anti-inflammatory cytokines. Efficacy of ROBs-QP was lost at 6.25 µM, with the exception of IL-6 production that was still potently inhibited.

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