| http://purl.uniprot.org/citations/21966468 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/21966468 | http://www.w3.org/2000/01/rdf-schema#comment | "Activation of the host antibacterial defenses by the toll-like receptors (TLR) also selectively activates energy-sensing and metabolic pathways, but the mechanisms are poorly understood. This includes the metabolic and mitochondrial biogenesis master co-activators, Ppargc1a (PGC-1α) and Ppargc1b (PGC-1β) in Staphylococcus aureus (S. aureus) sepsis. The expression of these genes in the liver is markedly attenuated inTLR2(-/-) mice and markedly accentuated in TLR4(-/-) mice compared with wild type (WT) mice. We sought to explain this difference by using specific TLR-pathway knockout mice to test the hypothesis that these co-activator genes are directly regulated through TLR2 signaling. By comparing their responses to S. aureus with WT mice, we found that MyD88-deficient and MAL-deficient mice expressed hepatic Ppargc1a and Ppargc1b normally, but that neither gene was activated in TRAM-deficient mice. Ppargc1a/b activation did not require NF-kβ, but did require an interferon response factor (IRF), because neither gene was activated in IRF-3/7 double-knockout mice in sepsis, but both were activated normally in Unc93b1-deficient (3d) mice. Nuclear IRF-7 levels in TLR2(-/-) and TLR4(-/-) mice decreased and increased respectively post-inoculation and IRF-7 DNA-binding at the Ppargc1a promoter was demonstrated by chromatin immunoprecipitation. Also, a TLR2-TLR4-TRAM native hepatic protein complex was detected by immunoprecipitation within 6 h of S. aureus inoculation that could support MyD88-independent signaling to Ppargc1a/b. Overall, these findings disclose a novel MyD88-independent pathway in S. aureus sepsis that links TLR2 and TLR4 signaling in innate immunity to Ppargc1a/b gene regulation in a critical metabolic organ, the liver, by means of TRAM, TRIF, and IRF-7."xsd:string |
| http://purl.uniprot.org/citations/21966468 | http://purl.org/dc/terms/identifier | "doi:10.1371/journal.pone.0025249"xsd:string |
| http://purl.uniprot.org/citations/21966468 | http://purl.uniprot.org/core/author | "Piantadosi C.A."xsd:string |
| http://purl.uniprot.org/citations/21966468 | http://purl.uniprot.org/core/author | "Suliman H.B."xsd:string |
| http://purl.uniprot.org/citations/21966468 | http://purl.uniprot.org/core/author | "Sweeney T.E."xsd:string |
| http://purl.uniprot.org/citations/21966468 | http://purl.uniprot.org/core/author | "Hollingsworth J.W."xsd:string |
| http://purl.uniprot.org/citations/21966468 | http://purl.uniprot.org/core/author | "Welty-Wolf K.E."xsd:string |
| http://purl.uniprot.org/citations/21966468 | http://purl.uniprot.org/core/date | "2011"xsd:gYear |
| http://purl.uniprot.org/citations/21966468 | http://purl.uniprot.org/core/name | "PLoS One"xsd:string |
| http://purl.uniprot.org/citations/21966468 | http://purl.uniprot.org/core/pages | "e25249"xsd:string |
| http://purl.uniprot.org/citations/21966468 | http://purl.uniprot.org/core/title | "A toll-like receptor 2 pathway regulates the Ppargc1a/b metabolic co-activators in mice with Staphylococcal aureus sepsis."xsd:string |
| http://purl.uniprot.org/citations/21966468 | http://purl.uniprot.org/core/volume | "6"xsd:string |
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