title: Broccoli-Derived Nanoparticle Inhibits Mouse Colitis by Activating Dendritic Cell AMP-Activated Protein Kinase.
abstract: 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.
authors.affiliation: Department of Microbiology & Immunology, James Graham Brown Cancer Center, University of Louisville, Louisville, KY 40202, USA.
authors.forename: Zhongbin
authors.initials: Z
authors.lastname: Deng
authors.affiliation: Department of Microbiology & Immunology, James Graham Brown Cancer Center, University of Louisville, Louisville, KY 40202, USA.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Rong
authors.affiliation: Department of Microbiology & Immunology, James Graham Brown Cancer Center, University of Louisville, Louisville, KY 40202, USA.
authors.forename: Yun
authors.initials: Y
authors.lastname: Teng
authors.affiliation: Department of Microbiology & Immunology, James Graham Brown Cancer Center, University of Louisville, Louisville, KY 40202, USA.
authors.forename: Jingyao
authors.initials: J
authors.lastname: Mu
authors.affiliation: Department of Microbiology & Immunology, James Graham Brown Cancer Center, University of Louisville, Louisville, KY 40202, USA.
authors.forename: Xiaoying
authors.initials: X
authors.lastname: Zhuang
authors.affiliation: Department of Anatomical Sciences and Neurobiology, University of Louisville, Louisville, KY 40202, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Tseng
authors.affiliation: Department of Microbiology & Immunology, James Graham Brown Cancer Center, University of Louisville, Louisville, KY 40202, USA.
authors.forename: Abhilash
authors.initials: A
authors.lastname: Samykutty
authors.affiliation: Department of Microbiology & Immunology, James Graham Brown Cancer Center, University of Louisville, Louisville, KY 40202, USA.
authors.forename: Lifeng
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Department of Microbiology & Immunology, James Graham Brown Cancer Center, University of Louisville, Louisville, KY 40202, USA.
authors.forename: Jun
authors.initials: J
authors.lastname: Yan
authors.affiliation: Department of Microbiology & Immunology, James Graham Brown Cancer Center, University of Louisville, Louisville, KY 40202, USA.
authors.forename: Donald
authors.initials: D
authors.lastname: Miller
authors.affiliation: Department of Microbiology & Immunology, James Graham Brown Cancer Center, University of Louisville, Louisville, KY 40202, USA.
authors.forename: Jill
authors.initials: J
authors.lastname: Suttles
authors.affiliation: Robley Rex VA Medical Center, Louisville, KY 40206, USA; Department of Microbiology & Immunology, James Graham Brown Cancer Center, University of Louisville, Louisville, KY 40202, USA. Electronic address: h0zhan17@louisville.edu.
authors.forename: Huang-Ge
authors.initials: HG
authors.lastname: Zhang
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000235:genetics* / Q000378:metabolism; D000284:Administration, Oral; D019264:Adoptive Transfer; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D001937:Brassica / Q000737:chemistry*; D003093:Colitis, Ulcerative / Q000139:chemically induced / Q000276:immunology / Q000473:pathology / Q000517:prevention & control*; D003713:Dendritic Cells / Q000187:drug effects* / Q000276:immunology / Q000473:pathology / Q000637:transplantation; D004195:Disease Models, Animal; D004789:Enzyme Activation / Q000187:drug effects; D015870:Gene Expression; D006801:Humans; D007108:Immune Tolerance; D017879:Isothiocyanates / Q000737:chemistry; D008055:Lipids / Q000302:isolation & purification / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D053758:Nanoparticles / Q000008:administration & dosage / Q000737:chemistry*; D010936:Plant Extracts / Q000737:chemistry; D012967:Sodium Dodecyl Sulfate; D013454:Sulfoxides
chemical_list: D000893:Anti-Inflammatory Agents; D017879:Isothiocyanates; D008055:Lipids; D010936:Plant Extracts; D013454:Sulfoxides; D012967:Sodium Dodecyl Sulfate; D055372:AMP-Activated Protein Kinases; C016766:sulforaphane
keywords: AMPK; broccoli nanoparticles; colitis; edible plant and mammalia; gut immune homeostasis; sulforaphane; tolerogenic DCs; transkingdom interaction