title: Prebiotic oligosaccharides reduce proinflammatory cytokines in intestinal Caco-2 cells via activation of PPARγ and peptidoglycan recognition protein 3.
abstract: Prebiotic oligosaccharides modulate the intestinal microbiota and beneficially affect the human body by reducing intestinal inflammation. This immunomodulatory effect was assumed to be bacterial in origin. However, some observations suggest that oligosaccharides may exert an antiinflammatory effect per se. We hypothesized that oligosaccharides affect the intestinal immunity via activation of peptidoglycan recognition protein 3 (PGlyRP3), which reduces the expression of proinflammatory cytokines. Caco-2 cells were treated with the oligosaccharides, α3-sialyllactose, or fructooligosaccharides (Raftilose p95), and the effects of these treatments on PGlyRP3 and PPARγ expression, the release and expression of some proinflammatory cytokines, and NF-κB translocation were tested. Both oligosaccharides had antiinflammatory activity; they significantly reduced IL-12 secretion in Caco-2 cells and gene expression of IL-12p35, IL-8, and TNFα. They also reduced the gene expression and nuclear translocation of NF-κB. Both oligosaccharides dose and time dependently induced the production of PGlyRP3, the silencing of which by transfection of Caco-2 cells with specific small interfering RNA targeting PGlyRP3 abolished the antiinflammatory role of both oligosaccharides. Incubation of Caco-2 cells with both oligosaccharides induced PPARγ. Antagonizing PPARγ by culturing the cells with GW9662 for 24 h inhibited the oligosaccharide-induced PGlyRP3 production and the antiinflammatory effect of the oligosaccharides. We conclude that oligosaccharides may exert an antiinflammatory effect by inducing the nuclear receptor PPARγ, which regulates the antiinflammatory PGlyRP3.
authors: Max Rubner Institute, 24103 Kiel, Germany. zenhomm@scientist.com.
authors: Marwa
authors: M
authors: Zenhom
authors: Ayman
authors: A
authors: Hyder
authors: Michael
authors: M
authors: de Vrese
authors: Knut J
authors: KJ
authors: Heller
authors: Thomas
authors: T
authors: Roeder
authors: Jürgen
authors: J
authors: Schrezenmeir
mesh_terms: D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000378:metabolism*; D018938:Caco-2 Cells; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D002467:Cell Nucleus / Q000378:metabolism; D016207:Cytokines / Q000235:genetics / Q000378:metabolism*; D015536:Down-Regulation / Q000187:drug effects; D020868:Gene Silencing; D006801:Humans; D056747:Immunomodulation; D007413:Intestinal Mucosa / Q000276:immunology / Q000378:metabolism*; D007444:Inulin / Q000008:administration & dosage / Q000031:analogs & derivatives; D009844:Oligosaccharides / Q000008:administration & dosage / Q000378:metabolism*; D047495:PPAR gamma / Q000037:antagonists & inhibitors / Q000378:metabolism*; D056692:Prebiotics; D021381:Protein Transport; D012333:RNA, Messenger / Q000378:metabolism; D034741:RNA, Small Interfering; D020133:Reverse Transcriptase Polymerase Chain Reaction; D051996:Transcription Factor RelA / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects
chemical_list: C421467:3'-sialyllactose; D000894:Anti-Inflammatory Agents, Non-Steroidal; D002352:Carrier Proteins; D016207:Cytokines; D009844:Oligosaccharides; D047495:PPAR gamma; D056692:Prebiotics; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D051996:Transcription Factor RelA; C118897:peptidoglycan recognition protein; D007444:Inulin