Bacterial lipoprotein-induced tolerance is reversed by overexpression of IRAK-1.
AffiliationDepartment of Academic Surgery, University College Cork (UCC)/National University of Ireland (NUI), Cork University Hospital, Cork, Ireland.
Gene Expression Regulation
Interleukin-1 Receptor-Associated Kinases
Toll-Like Receptor 2
Tumor Necrosis Factor-alpha
MetadataShow full item record
CitationBacterial lipoprotein-induced tolerance is reversed by overexpression of IRAK-1. 2012, 90 (3):314-20 Immunol. Cell Biol.
JournalImmunology and cell biology
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.
- [The influence of over expression of interleukin-1 receptor-associated kinase 1 on bacterial lipoprotein-induced tolerance].
- Authors: Li CH, Wang JJ, Gao LJ, Wang JH, Huang ZQ
- Issue date: 2010 Jan
- Bacterial lipoprotein-induced self-tolerance and cross-tolerance to LPS are associated with reduced IRAK-1 expression and MyD88-IRAK complex formation.
- Authors: Li CH, Wang JH, Redmond HP
- Issue date: 2006 Apr
- Induction of bacterial lipoprotein tolerance is associated with suppression of toll-like receptor 2 expression.
- Authors: Wang JH, Doyle M, Manning BJ, Di Wu Q, Blankson S, Redmond HP
- Issue date: 2002 Sep 27
- MicroRNA-146a is upregulated by and negatively regulates TLR2 signaling.
- Authors: Quinn EM, Wang JH, O'Callaghan G, Redmond HP
- Issue date: 2013
- ST2 negatively regulates TLR2 signaling, but is not required for bacterial lipoprotein-induced tolerance.
- Authors: Liu J, Buckley JM, Redmond HP, Wang JH
- Issue date: 2010 May 15