Show simple item record

dc.contributor.authorLi, Chong Hui
dc.contributor.authorLiu, Jinghua
dc.contributor.authorAn, Mingbang
dc.contributor.authorRedmond, H Paul
dc.contributor.authorWang, Jiang Huai
dc.date.accessioned2012-08-20T14:59:08Z
dc.date.available2012-08-20T14:59:08Z
dc.date.issued2012-03
dc.identifier.citationBacterial lipoprotein-induced tolerance is reversed by overexpression of IRAK-1. 2012, 90 (3):314-20 Immunol. Cell Biol.en_GB
dc.identifier.issn1440-1711
dc.identifier.pmid21537341
dc.identifier.doi10.1038/icb.2011.37
dc.identifier.urihttp://hdl.handle.net/10147/239195
dc.description.abstractTolerance to bacterial cell wall components including bacterial lipoprotein (BLP) represents an essential regulatory mechanism during bacterial infection. Reduced Toll-like receptor 2 (TLR2) and IL-1 receptor-associated kinase 1 (IRAK-1) expression is a characteristic of the downregulated TLR signaling pathway observed in BLP-tolerised cells. In this study, we attempted to clarify whether TLR2 and/or IRAK-1 are the key molecules responsible for BLP-induced tolerance. Transfection of HEK293 cells and THP-1 cells with the plasmid encoding TLR2 affected neither BLP tolerisation-induced NF-κB deactivation nor BLP tolerisation-attenuated pro-inflammatory cytokine tumor necrosis factor alpha (TNF-α) production, indicating that BLP tolerance develops despite overexpression of TLR2 in these cells. In contrast, overexpression of IRAK-1 reversed BLP-induced tolerance, as transfection of IRAK-1 expressing vector resulted in a dose-dependent NF-κB activation and TNF-α release in BLP-tolerised cells. Furthermore, BLP-tolerised cells exhibited markedly repressed NF-κB p65 phosphorylation and impaired binding of p65 to several pro-inflammatory cytokine gene promoters including TNF-α and interleukin-6 (IL-6). Overexpression of IRAK-1 restored the nuclear transactivation of p65 at both TNF-α and IL-6 promoters. These results indicate a crucial role for IRAK-1 in BLP-induced tolerance, and suggest IRAK-1 as a potential target for manipulation of the TLR-mediated inflammatory response during microbial sepsis.
dc.language.isoenen
dc.rightsArchived with thanks to Immunology and cell biologyen_GB
dc.subject.meshBacterial Proteins
dc.subject.meshCell Line
dc.subject.meshGene Expression Regulation
dc.subject.meshHumans
dc.subject.meshImmune Tolerance
dc.subject.meshInflammation Mediators
dc.subject.meshInterleukin-1 Receptor-Associated Kinases
dc.subject.meshInterleukin-6
dc.subject.meshLipoproteins
dc.subject.meshNF-kappa B
dc.subject.meshPhosphorylation
dc.subject.meshSepsis
dc.subject.meshSignal Transduction
dc.subject.meshToll-Like Receptor 2
dc.subject.meshTranscriptional Activation
dc.subject.meshTransgenes
dc.subject.meshTumor Necrosis Factor-alpha
dc.titleBacterial lipoprotein-induced tolerance is reversed by overexpression of IRAK-1.en_GB
dc.typeArticleen
dc.contributor.departmentDepartment of Academic Surgery, University College Cork (UCC)/National University of Ireland (NUI), Cork University Hospital, Cork, Ireland.en_GB
dc.identifier.journalImmunology and cell biologyen_GB
dc.description.provinceMunsteren
html.description.abstractTolerance to bacterial cell wall components including bacterial lipoprotein (BLP) represents an essential regulatory mechanism during bacterial infection. Reduced Toll-like receptor 2 (TLR2) and IL-1 receptor-associated kinase 1 (IRAK-1) expression is a characteristic of the downregulated TLR signaling pathway observed in BLP-tolerised cells. In this study, we attempted to clarify whether TLR2 and/or IRAK-1 are the key molecules responsible for BLP-induced tolerance. Transfection of HEK293 cells and THP-1 cells with the plasmid encoding TLR2 affected neither BLP tolerisation-induced NF-κB deactivation nor BLP tolerisation-attenuated pro-inflammatory cytokine tumor necrosis factor alpha (TNF-α) production, indicating that BLP tolerance develops despite overexpression of TLR2 in these cells. In contrast, overexpression of IRAK-1 reversed BLP-induced tolerance, as transfection of IRAK-1 expressing vector resulted in a dose-dependent NF-κB activation and TNF-α release in BLP-tolerised cells. Furthermore, BLP-tolerised cells exhibited markedly repressed NF-κB p65 phosphorylation and impaired binding of p65 to several pro-inflammatory cytokine gene promoters including TNF-α and interleukin-6 (IL-6). Overexpression of IRAK-1 restored the nuclear transactivation of p65 at both TNF-α and IL-6 promoters. These results indicate a crucial role for IRAK-1 in BLP-induced tolerance, and suggest IRAK-1 as a potential target for manipulation of the TLR-mediated inflammatory response during microbial sepsis.


This item appears in the following Collection(s)

Show simple item record