Bacterial lipoprotein-induced tolerance is reversed by overexpression of IRAK-1.

Hdl Handle:
http://hdl.handle.net/10147/239195
Title:
Bacterial lipoprotein-induced tolerance is reversed by overexpression of IRAK-1.
Authors:
Li, Chong Hui; Liu, Jinghua; An, Mingbang; Redmond, H Paul; Wang, Jiang Huai
Affiliation:
Department of Academic Surgery, University College Cork (UCC)/National University of Ireland (NUI), Cork University Hospital, Cork, Ireland.
Citation:
Bacterial lipoprotein-induced tolerance is reversed by overexpression of IRAK-1. 2012, 90 (3):314-20 Immunol. Cell Biol.
Journal:
Immunology and cell biology
Issue Date:
Mar-2012
URI:
http://hdl.handle.net/10147/239195
DOI:
10.1038/icb.2011.37
PubMed ID:
21537341
Abstract:
Tolerance 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.
Item Type:
Article
Language:
en
MeSH:
Bacterial Proteins; Cell Line; Gene Expression Regulation; Humans; Immune Tolerance; Inflammation Mediators; Interleukin-1 Receptor-Associated Kinases; Interleukin-6; Lipoproteins; NF-kappa B; Phosphorylation; Sepsis; Signal Transduction; Toll-Like Receptor 2; Transcriptional Activation; Transgenes; Tumor Necrosis Factor-alpha
ISSN:
1440-1711

Full metadata record

DC FieldValue Language
dc.contributor.authorLi, Chong Huien_GB
dc.contributor.authorLiu, Jinghuaen_GB
dc.contributor.authorAn, Mingbangen_GB
dc.contributor.authorRedmond, H Paulen_GB
dc.contributor.authorWang, Jiang Huaien_GB
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.en_GB
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
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