Thumbnail Image
Publication

Induction of bacterial lipoprotein tolerance is associated with suppression of toll-like receptor 2 expression.

Wang, Jiang Huai
; 
Doyle, Majella
; 
Manning, Brian J
; 
Di Wu, Qiong
; 
Blankson, Siobhan
; 
Redmond, H Paul
Citations
Altmetric:
Author
Wang, Jiang Huai
 Doyle, Majella
 Manning, Brian J
 Di Wu, Qiong
 Blankson, Siobhan
 Redmond, H Paul
Advisors
Editors
Other Contributors
Departments
Department of Academic Surgery, National University of Ireland, Cork University, Hospital, Cork, Ireland. jh.wang@ucc.ie
Date
2012-02-03T15:10:27Z
Date Submitted
Keywords
Other Subjects
Subject Mesh
Antigens, CD14/biosynthesis/metabolism
Bacterial Outer Membrane Proteins/*pharmacology
Blotting, Western
Cell Line
Cell Nucleus/metabolism
Cell Separation
Culture Media, Serum-Free/pharmacology
Cytokines/metabolism
Down-Regulation
*Drosophila Proteins
Flow Cytometry
Humans
*Immune Tolerance
Interleukin-6/metabolism
Lipopolysaccharides/metabolism/*pharmacology
Lipoproteins/*metabolism
Luciferases/metabolism
MAP Kinase Signaling System
Membrane Glycoproteins/*biosynthesis/metabolism
Microscopy, Fluorescence
Monocytes/immunology/metabolism
NF-kappa B/metabolism
Phosphorylation
Receptors, Cell Surface/*biosynthesis/metabolism
Toll-Like Receptor 2
Toll-Like Receptor 4
Toll-Like Receptors
Transfection
Tumor Necrosis Factor-alpha/metabolism
Planned Date
Start Date
Collaborators
Principal Investigators
Files
Thumbnail Image
1-s2.0-S0021925818365736-main.pdf
Adobe PDF, 480.49 KB
Alternative Titles
Publisher
URI
https://hdl.handle.net/10147/209033
Abstract
Tolerance 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.
Language
eng
Citation
J Biol Chem. 2002 Sep 27;277(39):36068-75. Epub 2002 Jul 19.
ISSN
0021-9258 (Print)
0021-9258 (Linking)
eISSN
ISBN
DOI
10.1074/jbc.M205584200
PMID
12133836
PMCID
Sponsorships
Funding Sources
Funding Amounts
Grant Identifiers
Methodology
Duration
Ethical Approval
Embedded videos