Prebiotic Oligosaccharides Reduce Proinflammatory Cytokines in Intestinal Caco-2 Cells via Activation of PPARγ and Peptidoglycan Recognition Protein 31–3

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.

Galacto-oligosaccharides exert a protective effect against heat stress in a Caco-2 cell model

“…Nevertheless, it remains to be completely elucidated whether there are significant differences in the biological activity of GOS related to the structures, molecular weight and type of glycosidic linkages. As yet it is only known that non-digestible oligosaccharides, like GOS, might interact with peptidoglycan recognition protein 3, peroxisome proliferatoractivated receptor γ or carbohydrate receptors, such as C-type lectin (Jeurink et al, 2013;Vos, M'Rabet, Stahl, Boehm, & Garssen, 2007;Zenhom et al, 2011). Furthermore, there might be a similarity between the protection of GOS against heat stress and the thermal protection of fungal species by accumulation of high levels of trehalose-based oligosaccharides (Wyatt et al, 2015).…”

Non-digestible carbohydrates in infant formula as substitution for human milk oligosaccharide functions: Effects on microbiota and gut maturation

“…Zenhom et al (2011) investigated the effect of FOS on the expression of the peptidoglycan recognition protein 3 (PGlyRP3) in an in vitro experiment using Caco-2 cells. Activation of this receptor reduces the expression of proinflammatory cytokines.…”

“…When Caco-2 cells were transfected with specific small interfering RNA targeting PGlyRP3, the anti-inflammatory effects of FOS, measured by cytokine release and expression and NF-kB translocation, were abolished. This might indicate that FOS exerts an anti-inflammatory effect by inducing nuclear PPARg, which regulates the anti-inflammatory PGlyPR3 (Zenhom et al 2011). FOS also has direct effects on gut barrier function.…”

Molecular cloning and functional characterization of peptidoglycan recognition protein 6 in grass carp Ctenopharyngodon idella

“…Initially, mammalian PGRPs were reported to have two major functions: amidase activity and antibacterial activity (Wang et al, 2003;Dziarski and Gupta, 2006). Recently, it has been suggested that mammalian PGRPs have a role in modulating inflammation and immune responses (Saha et al, 2009(Saha et al, , 2010Park et al, 2011;Zenhom et al, 2011).…”