Broccoli-Derived Nanoparticle Inhibits Mouse Colitis by Activating Dendritic Cell AMP-Activated Protein Kinase

The intestinal immune system is continuously exposed to massive amounts of nanoparticles derived from food. Whether nanoparticles from plants we eat daily have a role in maintaining intestinal immune homeostasis is poorly defined. Here, we present evidence supporting our hypothesis that edible nanop...

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Veröffentlicht in:Molecular therapy 2017-07, Vol.25 (7), p.1641-1654
Hauptverfasser: Deng, Zhongbin, Rong, Yuan, Teng, Yun, Mu, Jingyao, Zhuang, Xiaoying, Tseng, Michael, Samykutty, Abhilash, Zhang, Lifeng, Yan, Jun, Miller, Donald, Suttles, Jill, Zhang, Huang-Ge
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container_end_page 1654
container_issue 7
container_start_page 1641
container_title Molecular therapy
container_volume 25
creator Deng, Zhongbin
Rong, Yuan
Teng, Yun
Mu, Jingyao
Zhuang, Xiaoying
Tseng, Michael
Samykutty, Abhilash
Zhang, Lifeng
Yan, Jun
Miller, Donald
Suttles, Jill
Zhang, Huang-Ge
description The intestinal immune system is continuously exposed to massive amounts of nanoparticles derived from food. Whether nanoparticles from plants we eat daily have a role in maintaining intestinal immune homeostasis is poorly defined. Here, we present evidence supporting our hypothesis that edible nanoparticles regulate intestinal immune homeostasis by targeting dendritic cells (DCs). Using three mouse colitis models, our data show that orally given nanoparticles isolated from broccoli extracts protect mice against colitis. Broccoli-derived nanoparticle (BDN)-mediated activation of adenosine monophosphate-activated protein kinase (AMPK) in DCs plays a role in not only prevention of DC activation but also induction of tolerant DCs. Adoptively transferring DCs pre-pulsed with total BDN lipids, but not sulforaphane (SFN)-depleted BDN lipids, prevented DSS-induced colitis in C57BL/6 (B6) mice, supporting the role of BDN SFN in the induction of DC tolerance. Adoptively transferring AMPK+/+, but not AMPK−/−, DCs pre-pulsed with SFN prevented DSS-induced colitis in B6 mice, further supporting the DC AMPK role in SFN-mediated prevention of DSS-induced colitis. This finding could open new preventive or therapeutic avenues to address intestinal-related inflammatory diseases via activating AMPK. The intestinal immune system is continuously exposed to massive amounts of nanoparticles derived from food. As proof of concept, in this issue of Molecular Therapy, Deng et al. show that nanoparticles isolated from broccoli extracts protected mice from developing colitis by induction of tolerant dendritic cells through the adenosine monophosphate-activated protein kinase-mediated pathway.
doi_str_mv 10.1016/j.ymthe.2017.01.025
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Whether nanoparticles from plants we eat daily have a role in maintaining intestinal immune homeostasis is poorly defined. Here, we present evidence supporting our hypothesis that edible nanoparticles regulate intestinal immune homeostasis by targeting dendritic cells (DCs). Using three mouse colitis models, our data show that orally given nanoparticles isolated from broccoli extracts protect mice against colitis. Broccoli-derived nanoparticle (BDN)-mediated activation of adenosine monophosphate-activated protein kinase (AMPK) in DCs plays a role in not only prevention of DC activation but also induction of tolerant DCs. Adoptively transferring DCs pre-pulsed with total BDN lipids, but not sulforaphane (SFN)-depleted BDN lipids, prevented DSS-induced colitis in C57BL/6 (B6) mice, supporting the role of BDN SFN in the induction of DC tolerance. Adoptively transferring AMPK+/+, but not AMPK−/−, DCs pre-pulsed with SFN prevented DSS-induced colitis in B6 mice, further supporting the DC AMPK role in SFN-mediated prevention of DSS-induced colitis. This finding could open new preventive or therapeutic avenues to address intestinal-related inflammatory diseases via activating AMPK. The intestinal immune system is continuously exposed to massive amounts of nanoparticles derived from food. As proof of concept, in this issue of Molecular Therapy, Deng et al. show that nanoparticles isolated from broccoli extracts protected mice from developing colitis by induction of tolerant dendritic cells through the adenosine monophosphate-activated protein kinase-mediated pathway.</description><identifier>ISSN: 1525-0016</identifier><identifier>EISSN: 1525-0024</identifier><identifier>DOI: 10.1016/j.ymthe.2017.01.025</identifier><identifier>PMID: 28274798</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>Adenosine kinase ; Administration, Oral ; Adoptive Transfer ; AMP ; AMP-activated protein kinase ; AMP-Activated Protein Kinases - genetics ; AMP-Activated Protein Kinases - metabolism ; AMPK ; Animal models ; Animals ; Anti-Inflammatory Agents - chemistry ; Anti-Inflammatory Agents - metabolism ; Anti-Inflammatory Agents - pharmacology ; Brassica - chemistry ; broccoli nanoparticles ; Cell activation ; Colitis ; Colitis, Ulcerative - chemically induced ; Colitis, Ulcerative - immunology ; Colitis, Ulcerative - pathology ; Colitis, Ulcerative - prevention &amp; control ; Colon ; Cytokines ; Dendritic cells ; Dendritic Cells - drug effects ; Dendritic Cells - immunology ; Dendritic Cells - pathology ; Dendritic Cells - transplantation ; Disease Models, Animal ; Disease prevention ; edible plant and mammalia ; Enzyme Activation - drug effects ; Food ; Food plants ; Gene Expression ; gut immune homeostasis ; Homeostasis ; Humans ; Hypotheses ; Immune system ; Immune Tolerance ; Immunological tolerance ; Inflammatory bowel disease ; Inflammatory diseases ; Intestine ; Isothiocyanates - chemistry ; Kinases ; Lipids ; Lipids - isolation &amp; purification ; Lipids - pharmacology ; Lymphocytes ; Methods ; Mice ; Mice, Inbred C57BL ; Nanoparticles ; Nanoparticles - administration &amp; dosage ; Nanoparticles - chemistry ; Original ; Plant Extracts - chemistry ; Proteins ; Rodents ; Sodium Dodecyl Sulfate ; Sulforaphane ; tolerogenic DCs ; transkingdom interaction ; Tumor necrosis factor-TNF ; Vegetables</subject><ispartof>Molecular therapy, 2017-07, Vol.25 (7), p.1641-1654</ispartof><rights>2017 The American Society of Gene and Cell Therapy</rights><rights>Copyright © 2017 The American Society of Gene and Cell Therapy. 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Whether nanoparticles from plants we eat daily have a role in maintaining intestinal immune homeostasis is poorly defined. Here, we present evidence supporting our hypothesis that edible nanoparticles regulate intestinal immune homeostasis by targeting dendritic cells (DCs). Using three mouse colitis models, our data show that orally given nanoparticles isolated from broccoli extracts protect mice against colitis. Broccoli-derived nanoparticle (BDN)-mediated activation of adenosine monophosphate-activated protein kinase (AMPK) in DCs plays a role in not only prevention of DC activation but also induction of tolerant DCs. Adoptively transferring DCs pre-pulsed with total BDN lipids, but not sulforaphane (SFN)-depleted BDN lipids, prevented DSS-induced colitis in C57BL/6 (B6) mice, supporting the role of BDN SFN in the induction of DC tolerance. 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Adoptively transferring AMPK+/+, but not AMPK−/−, DCs pre-pulsed with SFN prevented DSS-induced colitis in B6 mice, further supporting the DC AMPK role in SFN-mediated prevention of DSS-induced colitis. This finding could open new preventive or therapeutic avenues to address intestinal-related inflammatory diseases via activating AMPK. The intestinal immune system is continuously exposed to massive amounts of nanoparticles derived from food. As proof of concept, in this issue of Molecular Therapy, Deng et al. show that nanoparticles isolated from broccoli extracts protected mice from developing colitis by induction of tolerant dendritic cells through the adenosine monophosphate-activated protein kinase-mediated pathway.</abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>28274798</pmid><doi>10.1016/j.ymthe.2017.01.025</doi><tpages>14</tpages><oa>free_for_read</oa></addata></record>
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language eng
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source MEDLINE; PubMed Central; Alma/SFX Local Collection; EZB Electronic Journals Library
subjects Adenosine kinase
Administration, Oral
Adoptive Transfer
AMP
AMP-activated protein kinase
AMP-Activated Protein Kinases - genetics
AMP-Activated Protein Kinases - metabolism
AMPK
Animal models
Animals
Anti-Inflammatory Agents - chemistry
Anti-Inflammatory Agents - metabolism
Anti-Inflammatory Agents - pharmacology
Brassica - chemistry
broccoli nanoparticles
Cell activation
Colitis
Colitis, Ulcerative - chemically induced
Colitis, Ulcerative - immunology
Colitis, Ulcerative - pathology
Colitis, Ulcerative - prevention & control
Colon
Cytokines
Dendritic cells
Dendritic Cells - drug effects
Dendritic Cells - immunology
Dendritic Cells - pathology
Dendritic Cells - transplantation
Disease Models, Animal
Disease prevention
edible plant and mammalia
Enzyme Activation - drug effects
Food
Food plants
Gene Expression
gut immune homeostasis
Homeostasis
Humans
Hypotheses
Immune system
Immune Tolerance
Immunological tolerance
Inflammatory bowel disease
Inflammatory diseases
Intestine
Isothiocyanates - chemistry
Kinases
Lipids
Lipids - isolation & purification
Lipids - pharmacology
Lymphocytes
Methods
Mice
Mice, Inbred C57BL
Nanoparticles
Nanoparticles - administration & dosage
Nanoparticles - chemistry
Original
Plant Extracts - chemistry
Proteins
Rodents
Sodium Dodecyl Sulfate
Sulforaphane
tolerogenic DCs
transkingdom interaction
Tumor necrosis factor-TNF
Vegetables
title Broccoli-Derived Nanoparticle Inhibits Mouse Colitis by Activating Dendritic Cell AMP-Activated Protein Kinase
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