title: PPARγ-dependent peptidoglycan recognition protein 3 (PGlyRP3) expression regulates proinflammatory cytokines by microbial and dietary fatty acids.
abstract: PGlyRPs recognize bacterial peptidoglycan and function in antibacterial innate immunity. Focusing on the interference between nutrition and recognition pattern proteins, free fatty acids (FFA) of dietary and bacterial sources may exert their immunological response through modulating the expression level of the PGlyRPs in enterocytes. PGlyRP3 was the only PGlyRPs member expressed in Caco2 cells. In silico analysis showed that the promoter of PGlyRP3 has some PPRE regions that, as tested by EMSA, bind physically to the PPARγ-RXRα complex. PGlyRP3 gene expression was induced by PPARγ ligands including GW1929 and some FFA. Overexpression of PGlyRP3 in Caco2 cells down regulated the expression of the inflammatory cytokines IL-8, IL-12 and TNF-α, while its silencing increased the expression of these cytokines. FFA that induced the PGlyRP3 inhibited the tested cytokines. Silencing of PGlyRP3 gene caused the same FFA to increase the cytokine gene expression. A negative regulation of NF-κB pathway, including up-regulation of Iκβ-α and down regulation of NF-κB and COX-2, is involved in the anti-inflammatory effects of PGlyRP3. In conclusion, PPARγ mediates a modulation of PGlyRP3 gene expression, which is involved in inhibiting inflammation through negative regulation of NF-κB pathway.
authors.affiliation: Department of Physiology and Biochemistry of Nutrition, Max Rubner Institute, Hermann Weigmann Str. 1, 24103 Kiel, Germany. zenhomm@scientist.com
authors.forename: Marwa
authors.initials: M
authors.lastname: Zenhom
authors.forename: Ayman
authors.initials: A
authors.lastname: Hyder
authors.forename: Ina
authors.initials: I
authors.lastname: Kraus-Stojanowic
authors.forename: Annegret
authors.initials: A
authors.lastname: Auinger
authors.forename: Thomas
authors.initials: T
authors.lastname: Roeder
authors.forename: Jürgen
authors.initials: J
authors.lastname: Schrezenmeir
mesh_terms: D001577:Benzophenones / Q000494:pharmacology; D018938:Caco-2 Cells; D002352:Carrier Proteins / Q000235:genetics* / Q000378:metabolism*; D016207:Cytokines / Q000235:genetics / Q000378:metabolism*; D005227:Fatty Acids / Q000494:pharmacology*; D005786:Gene Expression Regulation / Q000187:drug effects / Q000235:genetics; D006801:Humans; D007249:Inflammation / Q000276:immunology* / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism; D047495:PPAR gamma / Q000819:agonists / Q000378:metabolism*; D011401:Promoter Regions, Genetic / Q000235:genetics; D047490:Retinoid X Receptor alpha / Q000378:metabolism; D015398:Signal Transduction; D014443:Tyrosine / Q000031:analogs & derivatives / Q000494:pharmacology
chemical_list: D001577:Benzophenones; D002352:Carrier Proteins; D016207:Cytokines; D005227:Fatty Acids; D016328:NF-kappa B; D047495:PPAR gamma; D047490:Retinoid X Receptor alpha; C118897:peptidoglycan recognition protein; D014443:Tyrosine; C120099:GW 1929