PGlyRP3 concerts with PPARγ to attenuate DSS-induced colitis in mice.

Abstract

Nutrients may modulate immunity through their transcription factors that act on both metabolic and immunity genes. It has been shown that the transcription factor of lipid ligands PPARγ physically binds the gene promoter of the peptidoglycan recognition protein (PGlyRP3), which showed anti-inflammatory action in vitro. It is hypothesized in the present work that olive oil feeding protects against toxicity of DSS-induced colitis via activation of the lipid transcription factor PPARγ that stimulates the anti-inflammatory PGlyRP3. Results: PGlyRP3 is expressed in mouse colon and up-regulated by olive oil feeding. Olive oil reduced mortality and severity scores of DSS-induced colitis and down-regulated the proinflammatory IL-1b, IL-6 and TNFα genes. This protective effect was accompanied by up-regulation of both PPARγ and PGlyRP3. Inhibition of PPARγ by its antagonist BADGE down-regulated PGlyRP3 and abolished the anti-inflammatory effect of olive oil feeding in this DSS-induced colitis model, reflecting the pivotal role of PPARγ binding nutrition and inflammation. Activation of PGlyRP3 by its ligand peptidoglycan was not responsible for the inflammation caused by peptidoglycan, since neutralization of TLR2 attenuated this inflammatory response without affecting the peptidoglycan-induced PGlyRP3 level. Olive oil activated the IκBα and inhibited NF-κB and cox-2 gene expressions, and p65 nuclear translocation in DSS-colitis mice, reflecting the involvement of the inhibition of NF-κB signaling pathway in the anti-inflammatory olive oil - PPARγ - PGlyRP3 access. This pathway was reactivated by the PPARγ antagonist BADGE. Conclusions: Olive oil regulates by the same transcription factor (PPARγ) both lipid metabolic and immune gene (PGlyRP3) expressions, exerting the anti-inflammatory effect, and protecting against DSS-induced colitis in mice.