Bacterial lipoprotein-induced self-tolerance and cross-tolerance to LPS are associated with reduced IRAK-1 expression and MyD88-IRAK complex formation.

Hdl Handle:
http://hdl.handle.net/10147/208865
Title:
Bacterial lipoprotein-induced self-tolerance and cross-tolerance to LPS are associated with reduced IRAK-1 expression and MyD88-IRAK complex formation.
Authors:
Li, Chong Hui; Wang, Jiang Huai; Redmond, H Paul
Affiliation:
Department of Academic Surgery, National University of Ireland (NUI)/University, College Cork, Cork University Hospital, Cork, Ireland.
Citation:
J Leukoc Biol. 2006 Apr;79(4):867-75. Epub 2006 Feb 3.
Journal:
Journal of leukocyte biology
Issue Date:
3-Feb-2012
URI:
http://hdl.handle.net/10147/208865
DOI:
10.1189/jlb.0905505
PubMed ID:
16461741
Abstract:
Tolerance to bacterial cell-wall components may represent an essential regulatory mechanism during bacterial infection. We have demonstrated previously that the inhibition of nuclear factor (NF)-kappaB and mitogen-activated protein kinase activation was present in bacterial lipoprotein (BLP) self-tolerance and its cross-tolerance to lipopolysaccharide (LPS). In this study, the effect of BLP-induced tolerance on the myeloid differentiation factor 88 (MyD88)-dependent upstream signaling pathway for NF-kappaB activation in vitro was examined further. When compared with nontolerant human monocytic THP-1 cells, BLP-tolerant cells had a significant reduction in tumor necrosis factor alpha (TNF-alpha) production in response to a high-dose BLP (86+/-12 vs. 6042+/-245 ng/ml, P < 0.01) or LPS (341+/-36 vs. 7882+/-318 ng/ml, P < 0.01) stimulation. The expression of Toll-like receptor 2 (TLR2) protein was down-regulated in BLP-tolerant cells, whereas no significant differences in TLR4, MyD88, interleukin-1 receptor-associated kinase 4 (IRAK-4), and TNF receptor-associated factor 6 expression were observed between nontolerant and BLP-tolerant cells, as confirmed by Western blot analysis. The IRAK-1 protein was reduced markedly in BLP-tolerant cells, although IRAK-1 mRNA expression remained unchanged as revealed by real-time reverse transcriptase-polymerase chain reaction analysis. Furthermore, decreased MyD88-IRAK immunocomplex formation, as demonstrated by immunoprecipitation, was observed in BLP-tolerant cells following a second BLP or LPS stimulation. BLP pretreatment also resulted in a marked inhibition in total and phosphorylated inhibitor of kappaB-alpha (IkappaB-alpha) expression, which was not up-regulated by subsequent BLP or LPS stimulation. These results demonstrate that in addition to the down-regulation of TLR2 expression, BLP tolerance is associated with a reduction in IRAK-1 expression, MyD88-IRAK association, and IkappaB-alpha phosphorylation. These findings further elucidate the molecular mechanisms underlying bacterial peptide tolerance.
Language:
eng
MeSH:
Adaptor Proteins, Signal Transducing/biosynthesis/*drug effects; Cell Line; Cells, Cultured; Humans; Immune Tolerance/*drug effects/immunology; Interleukin-1 Receptor-Associated Kinases; Intracellular Signaling Peptides and Proteins/*drug effects; Lipopolysaccharides/*antagonists & inhibitors/pharmacology; Lipoproteins/*pharmacology; Monocytes/*drug effects/immunology/metabolism; Multiprotein Complexes/biosynthesis/immunology; Myeloid Differentiation Factor 88; Neoplasm Proteins/biosynthesis/drug effects; Protein-Serine-Threonine Kinases/biosynthesis/*drug effects; RNA, Messenger/biosynthesis/drug effects; Signal Transduction/drug effects/immunology; Time Factors; Toll-Like Receptor 2/biosynthesis/drug effects; Toll-Like Receptor 4/biosynthesis/drug effects; Tumor Necrosis Factor-alpha/biosynthesis/drug effects
ISSN:
0741-5400 (Print); 0741-5400 (Linking)

Full metadata record

DC FieldValue Language
dc.contributor.authorLi, Chong Huien_GB
dc.contributor.authorWang, Jiang Huaien_GB
dc.contributor.authorRedmond, H Paulen_GB
dc.date.accessioned2012-02-03T15:05:51Z-
dc.date.available2012-02-03T15:05:51Z-
dc.date.issued2012-02-03T15:05:51Z-
dc.identifier.citationJ Leukoc Biol. 2006 Apr;79(4):867-75. Epub 2006 Feb 3.en_GB
dc.identifier.issn0741-5400 (Print)en_GB
dc.identifier.issn0741-5400 (Linking)en_GB
dc.identifier.pmid16461741en_GB
dc.identifier.doi10.1189/jlb.0905505en_GB
dc.identifier.urihttp://hdl.handle.net/10147/208865-
dc.description.abstractTolerance to bacterial cell-wall components may represent an essential regulatory mechanism during bacterial infection. We have demonstrated previously that the inhibition of nuclear factor (NF)-kappaB and mitogen-activated protein kinase activation was present in bacterial lipoprotein (BLP) self-tolerance and its cross-tolerance to lipopolysaccharide (LPS). In this study, the effect of BLP-induced tolerance on the myeloid differentiation factor 88 (MyD88)-dependent upstream signaling pathway for NF-kappaB activation in vitro was examined further. When compared with nontolerant human monocytic THP-1 cells, BLP-tolerant cells had a significant reduction in tumor necrosis factor alpha (TNF-alpha) production in response to a high-dose BLP (86+/-12 vs. 6042+/-245 ng/ml, P < 0.01) or LPS (341+/-36 vs. 7882+/-318 ng/ml, P < 0.01) stimulation. The expression of Toll-like receptor 2 (TLR2) protein was down-regulated in BLP-tolerant cells, whereas no significant differences in TLR4, MyD88, interleukin-1 receptor-associated kinase 4 (IRAK-4), and TNF receptor-associated factor 6 expression were observed between nontolerant and BLP-tolerant cells, as confirmed by Western blot analysis. The IRAK-1 protein was reduced markedly in BLP-tolerant cells, although IRAK-1 mRNA expression remained unchanged as revealed by real-time reverse transcriptase-polymerase chain reaction analysis. Furthermore, decreased MyD88-IRAK immunocomplex formation, as demonstrated by immunoprecipitation, was observed in BLP-tolerant cells following a second BLP or LPS stimulation. BLP pretreatment also resulted in a marked inhibition in total and phosphorylated inhibitor of kappaB-alpha (IkappaB-alpha) expression, which was not up-regulated by subsequent BLP or LPS stimulation. These results demonstrate that in addition to the down-regulation of TLR2 expression, BLP tolerance is associated with a reduction in IRAK-1 expression, MyD88-IRAK association, and IkappaB-alpha phosphorylation. These findings further elucidate the molecular mechanisms underlying bacterial peptide tolerance.en_GB
dc.language.isoengen_GB
dc.subject.meshAdaptor Proteins, Signal Transducing/biosynthesis/*drug effectsen_GB
dc.subject.meshCell Lineen_GB
dc.subject.meshCells, Cultureden_GB
dc.subject.meshHumansen_GB
dc.subject.meshImmune Tolerance/*drug effects/immunologyen_GB
dc.subject.meshInterleukin-1 Receptor-Associated Kinasesen_GB
dc.subject.meshIntracellular Signaling Peptides and Proteins/*drug effectsen_GB
dc.subject.meshLipopolysaccharides/*antagonists & inhibitors/pharmacologyen_GB
dc.subject.meshLipoproteins/*pharmacologyen_GB
dc.subject.meshMonocytes/*drug effects/immunology/metabolismen_GB
dc.subject.meshMultiprotein Complexes/biosynthesis/immunologyen_GB
dc.subject.meshMyeloid Differentiation Factor 88en_GB
dc.subject.meshNeoplasm Proteins/biosynthesis/drug effectsen_GB
dc.subject.meshProtein-Serine-Threonine Kinases/biosynthesis/*drug effectsen_GB
dc.subject.meshRNA, Messenger/biosynthesis/drug effectsen_GB
dc.subject.meshSignal Transduction/drug effects/immunologyen_GB
dc.subject.meshTime Factorsen_GB
dc.subject.meshToll-Like Receptor 2/biosynthesis/drug effectsen_GB
dc.subject.meshToll-Like Receptor 4/biosynthesis/drug effectsen_GB
dc.subject.meshTumor Necrosis Factor-alpha/biosynthesis/drug effectsen_GB
dc.titleBacterial lipoprotein-induced self-tolerance and cross-tolerance to LPS are associated with reduced IRAK-1 expression and MyD88-IRAK complex formation.en_GB
dc.contributor.departmentDepartment of Academic Surgery, National University of Ireland (NUI)/University, College Cork, Cork University Hospital, Cork, Ireland.en_GB
dc.identifier.journalJournal of leukocyte biologyen_GB
dc.description.provinceMunster-
All Items in Lenus, The Irish Health Repository are protected by copyright, with all rights reserved, unless otherwise indicated.