Induction of bacterial lipoprotein tolerance is associated with suppression of toll-like receptor 2 expression.
AffiliationDepartment of Academic Surgery, National University of Ireland, Cork University, Hospital, Cork, Ireland. firstname.lastname@example.org
Bacterial Outer Membrane Proteins/*pharmacology
Culture Media, Serum-Free/pharmacology
MAP Kinase Signaling System
Receptors, Cell Surface/*biosynthesis/metabolism
Toll-Like Receptor 2
Toll-Like Receptor 4
Tumor Necrosis Factor-alpha/metabolism
MetadataShow full item record
CitationJ Biol Chem. 2002 Sep 27;277(39):36068-75. Epub 2002 Jul 19.
JournalThe Journal of biological chemistry
AbstractTolerance to bacterial cell wall components including lipopolysaccharide (LPS) may represent an essential regulatory mechanism during bacterial infection. Two members of the Toll-like receptor (TLR) family, TLR2 and TLR4, recognize the specific pattern of bacterial cell wall components. TLR4 has been found to be responsible for LPS tolerance. However, the role of TLR2 in bacterial lipoprotein (BLP) tolerance and LPS tolerance is unclear. Pretreatment of human THP-1 monocytic cells with a synthetic bacterial lipopeptide induced tolerance to a second BLP challenge with diminished tumor necrosis factor-alpha and interleukin-6 production, termed BLP tolerance. Furthermore, BLP-tolerized THP-1 cells no longer responded to LPS stimulation, indicating a cross-tolerance to LPS. Induction of BLP tolerance was CD14-independent, as THP-1 cells that lack membrane-bound CD14 developed tolerance both in serum-free conditions and in the presence of a specific CD14 blocking monoclonal antibody (MEM-18). Pre-exposure of THP-1 cells to BLP suppressed mitogen-activated protein kinase phosphorylation and nuclear factor-kappaB activation in response to subsequent BLP and LPS stimulation, which is comparable with that found in LPS-tolerized cells, indicating that BLP tolerance and LPS tolerance may share similar intracellular pathways. However, BLP strongly enhanced TLR2 expression in non-tolerized THP-1 cells, whereas LPS stimulation had no effect. Furthermore, a specific TLR2 blocking monoclonal antibody (2392) attenuated BLP-induced, but not LPS-induced, tumor necrosis factor-alpha and interleukin-6 production, indicating BLP rather than LPS as a ligand for TLR2 engagement and activation. More importantly, pretreatment of THP-1 cells with BLP strongly inhibited TLR2 activation in response to subsequent BLP stimulation. In contrast, LPS tolerance did not prevent BLP-induced TLR2 overexpression. These results demonstrate that BLP tolerance develops through down-regulation of TLR2 expression.
- 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
- Overexpression of CD14, TLR4, and MD-2 in HEK 293T cells does not prevent induction of in vitro endotoxin tolerance.
- Authors: Medvedev AE, Vogel SN
- Issue date: 2003
- Expression and involvement of Toll-like receptors (TLR)2, TLR4, and CD14 in monocyte TNF-alpha production induced by lipopolysaccharides from Neisseria meningitidis.
- Authors: Mirlashari MR, Lyberg T
- Issue date: 2003 Aug
- Modulation of the lipopolysaccharide receptor complex (CD14, TLR4, MD-2) and toll-like receptor 2 in systemic inflammatory response syndrome-positive patients with and without infection: relationship to tolerance.
- Authors: Calvano JE, Agnese DM, Um JY, Goshima M, Singhal R, Coyle SM, Reddell MT, Kumar A, Calvano SE, Lowry SF
- Issue date: 2003 Nov
- Heat shock up-regulates expression of Toll-like receptor-2 and Toll-like receptor-4 in human monocytes via p38 kinase signal pathway.
- Authors: Zhou J, An H, Xu H, Liu S, Cao X
- Issue date: 2005 Apr