PPARγ-dependent peptidoglycan recognition protein 3 (PGlyRP3) expression regulates proinflammatory cytokines by microbial and dietary fatty acids
| Autor: | Ayman Hyder, Marwa Zenhom, Annegret Auinger, Jürgen Schrezenmeir, Ina Kraus-Stojanowic, Thomas Roeder |
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| Rok vydání: | 2010 |
| Předmět: |
Immunology
Inflammation Biology Proinflammatory cytokine chemistry.chemical_compound Benzophenones Downregulation and upregulation Gene expression medicine Immunology and Allergy Gene silencing Humans Promoter Regions Genetic Gene Innate immune system Retinoid X Receptor alpha Fatty Acids NF-kappa B Hematology PPAR gamma chemistry Biochemistry Gene Expression Regulation Cytokines Tyrosine Peptidoglycan medicine.symptom Caco-2 Cells Carrier Proteins Signal Transduction |
| Zdroj: | Immunobiology. 216(6) |
| ISSN: | 1878-3279 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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