Limits...
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.

Show MeSH

Related in: MedlinePlus

ROB-embedded polyphenol mix interferes with production of LPS-mediated cytokines from DCs.ROB-embedded piperine (ROBs-P), quercetin (ROBs-Q) or a mix of the two (ROBs-QP) were administered on day 5 and 7 [25 µM] to DC cultures. LPS [1 µg/ml] was administered on day 8. SNs were collected 24 h later and TNFα and IL-6 content evaluated by ELISA. Data are shown as mean ± S.D. of five independent experiments; **P<0.01, ***P<0.001.
© Copyright Policy
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC3928302&req=5

pone-0088898-g003: ROB-embedded polyphenol mix interferes with production of LPS-mediated cytokines from DCs.ROB-embedded piperine (ROBs-P), quercetin (ROBs-Q) or a mix of the two (ROBs-QP) were administered on day 5 and 7 [25 µM] to DC cultures. LPS [1 µg/ml] was administered on day 8. SNs were collected 24 h later and TNFα and IL-6 content evaluated by ELISA. Data are shown as mean ± S.D. of five independent experiments; **P<0.01, ***P<0.001.

Mentions: BMDCs were exposed to several ROBs-QP concentrations to address potential toxicity of the treatment. We observed a significant increase in apoptosis when DCs were treated with 100 µM of ROBs-QP. The percentage of apoptotic DCs obtained from 25 µM ROBs-QP treated wells was always below 18% and never significantly higher than the percentage of apoptotic cells observed in the untreated wells (data not shown). BMDCs were exposed to 25 µM of ROBs-embedded quercetin or piperine (ROBs-Q or ROBs-P, respectively), or ROBs containing the combination of the two polyphenols (ROBs-QP) at the same concentrations. Our results showed that ROBs-QP efficiently inhibited TNFα and IL-6 production (Fig. 3). Of note, ROBs-QP did not affect production of cytokines since cytokine production was comparable to untreated DCs in the absence of TLR4 engagement by LPS. Empty ROBs failed to decrease TNFα and IL-6 protein levels, revealing that the polyphenol content, and not the protective shell, was responsible for inhibition of inflammatory cytokine production (Fig. 3). To exclude eventual induction of cells proliferation, we collected and counted the cells following the supernatant collection. DCs proliferation was never observed (data not shown).


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)

ROB-embedded polyphenol mix interferes with production of LPS-mediated cytokines from DCs.ROB-embedded piperine (ROBs-P), quercetin (ROBs-Q) or a mix of the two (ROBs-QP) were administered on day 5 and 7 [25 µM] to DC cultures. LPS [1 µg/ml] was administered on day 8. SNs were collected 24 h later and TNFα and IL-6 content evaluated by ELISA. Data are shown as mean ± S.D. of five independent experiments; **P<0.01, ***P<0.001.
© Copyright Policy
Related In: Results  -  Collection

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

pone-0088898-g003: ROB-embedded polyphenol mix interferes with production of LPS-mediated cytokines from DCs.ROB-embedded piperine (ROBs-P), quercetin (ROBs-Q) or a mix of the two (ROBs-QP) were administered on day 5 and 7 [25 µM] to DC cultures. LPS [1 µg/ml] was administered on day 8. SNs were collected 24 h later and TNFα and IL-6 content evaluated by ELISA. Data are shown as mean ± S.D. of five independent experiments; **P<0.01, ***P<0.001.
Mentions: BMDCs were exposed to several ROBs-QP concentrations to address potential toxicity of the treatment. We observed a significant increase in apoptosis when DCs were treated with 100 µM of ROBs-QP. The percentage of apoptotic DCs obtained from 25 µM ROBs-QP treated wells was always below 18% and never significantly higher than the percentage of apoptotic cells observed in the untreated wells (data not shown). BMDCs were exposed to 25 µM of ROBs-embedded quercetin or piperine (ROBs-Q or ROBs-P, respectively), or ROBs containing the combination of the two polyphenols (ROBs-QP) at the same concentrations. Our results showed that ROBs-QP efficiently inhibited TNFα and IL-6 production (Fig. 3). Of note, ROBs-QP did not affect production of cytokines since cytokine production was comparable to untreated DCs in the absence of TLR4 engagement by LPS. Empty ROBs failed to decrease TNFα and IL-6 protein levels, revealing that the polyphenol content, and not the protective shell, was responsible for inhibition of inflammatory cytokine production (Fig. 3). To exclude eventual induction of cells proliferation, we collected and counted the cells following the supernatant collection. DCs proliferation was never observed (data not shown).

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