| http://purl.uniprot.org/citations/23264652 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/23264652 | http://www.w3.org/2000/01/rdf-schema#comment | "Innate immune response is the first defense against pathogens via recognition by various conserved pattern recognition receptors, such as TLRs, to initiate a rapid and strong cytokine alarm. TLR signaling-mediated cytokine production must be properly regulated to prevent pathological conditions deriving from overproduction of cytokines. In this study, the role of specific microRNAs in TLR-signaling pathway was investigated to reveal the cross-interaction and -regulation in the MyD88 pathway. In peptidoglycan (PGN)/TLR2-stimulated THP-1 monocytes, PBMCs, and primary macrophages showed rapid and dramatic miR-132 and miR-212 (miR-132/-212) upregulation. This newly identified response appeared earlier in time than the characteristic miR-146a response in LPS-TLR4 stimulation. The rapid induction of miR-132/-212 was transcription factor CREB dependent, and the sustained expression of miR-132/-212 was responsible for inducing tolerance to subsequent PGN challenge. Cross-tolerance was observed by TLR5 ligand flagellin and heat-killed or live bacteria resulting from miR-132/-212 upregulation. Mechanistically, IRAK4 was identified and validated as a target of miR-132/-212 by luciferase reporter assay and seed-sequence mutagenesis of the reporter. Transfection of miR-132 or miR-212 alone mimicked PGN tolerance in monocytes, whereas transfected specific miRNA inhibitors tampered the tolerance effect. During bacterial infection, PGN-mediated TLR2 signaling induces miR-132/-212 to downregulate IRAK4, an early component in the MyD88-dependent pathway, whereas LPS/TLR4-induced miR-146a downregulates downstream components of the same MyD88-dependent pathway. The identification of miR-132/-212 and miR-146a together to prevent damaging consequences from the overproduction of proinflammatory cytokines by targeting a common signaling pathway is significant and will provide insights into future design and development of therapeutics."xsd:string |
| http://purl.uniprot.org/citations/23264652 | http://purl.org/dc/terms/identifier | "doi:10.4049/jimmunol.1103060"xsd:string |
| http://purl.uniprot.org/citations/23264652 | http://purl.uniprot.org/core/author | "Yao B."xsd:string |
| http://purl.uniprot.org/citations/23264652 | http://purl.uniprot.org/core/author | "Satoh M."xsd:string |
| http://purl.uniprot.org/citations/23264652 | http://purl.uniprot.org/core/author | "Chan E.K."xsd:string |
| http://purl.uniprot.org/citations/23264652 | http://purl.uniprot.org/core/author | "Nahid M.A."xsd:string |
| http://purl.uniprot.org/citations/23264652 | http://purl.uniprot.org/core/author | "Kesavalu L."xsd:string |
| http://purl.uniprot.org/citations/23264652 | http://purl.uniprot.org/core/author | "Dominguez-Gutierrez P.R."xsd:string |
| http://purl.uniprot.org/citations/23264652 | http://purl.uniprot.org/core/date | "2013"xsd:gYear |
| http://purl.uniprot.org/citations/23264652 | http://purl.uniprot.org/core/name | "J Immunol"xsd:string |
| http://purl.uniprot.org/citations/23264652 | http://purl.uniprot.org/core/pages | "1250-1263"xsd:string |
| http://purl.uniprot.org/citations/23264652 | http://purl.uniprot.org/core/title | "Regulation of TLR2-mediated tolerance and cross-tolerance through IRAK4 modulation by miR-132 and miR-212."xsd:string |
| http://purl.uniprot.org/citations/23264652 | http://purl.uniprot.org/core/volume | "190"xsd:string |
| http://purl.uniprot.org/citations/23264652 | http://www.w3.org/2004/02/skos/core#exactMatch | http://purl.uniprot.org/pubmed/23264652 |
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