Prebiotic Oligosaccharides Reduce Proinflammatory Cytokines in Intestinal Caco-2 Cells via Activation of PPARγ and Peptidoglycan Recognition Protein 31–31,2

https://doi.org/10.3945/jn.110.136176Get rights and content
Under an Elsevier user license
open archive

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-ĸB 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-ĸB. 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 PPARƳ. 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 PPARƳ, which regulates the antiinflammatory PGlyRP3.

Abbreviations used:

DC
dendritic cell
FOS
fructooligosaccharide
MEM
Minimum Essential Medium
siRNA
small interfering RNA
Th
T helper
TLR
Toll-like receptor

Cited by (0)

1

Supported by the PhD grant from GALAB Technologies GmbH, Geesthacht, Germany, to Marwa Zenhom and by Foerderer und Freunde der BafM, Kiel, Germany.

2

Author disclosures: M. Zenhom, A. Hyder, M. de Vrese, K. J. Heller, T. Roeder, and J. Schrezenmeir, no conflicts of interest.