Differential gene expression of interleukin-1 receptor associated kinase-1 and interleukin-1 receptor associated kinase-M in peripheral blood mononuclear cells of young and aged rats following preconditioning with endotoxin.
Shock
; 31(1): 55-63, 2009 Jan.
Article
in En
| MEDLINE
| ID: mdl-18497707
ABSTRACT
The IL-1 receptor-associated kinase 1 (IRAK-1) and IRAK-M are key signaling molecules in cellular responses to endotoxin initiated through the Toll-like receptors (TLRs). The aim of this study was to evaluate the effect of age on the modulation of TLRs and IRAK-1 and IRAK-M in peripheral blood mononuclear cells (PBMCs) exposed in vitro to endotoxin under conditions that could induce endotoxin tolerance. Peripheral blood mononuclear cells obtained from young (4- to 6-month-old) and aged (24- to 26-month-old) Brown Norway rats were treated with high-dose LPS, with or without priming with low-dose LPS. In comparison with younger rats, the intensity of TLR-4 expression was persistently high in monocytes from aged rats after stimulation with LPS and was not decreased by priming with low-dose LPS (P < 0.05). Messenger RNA (mRNA) for TLR-4 in PBMCs from aged rats did not show any decrease after priming with low-dose LPS as seen in PBMCs from young rats at 24 h (P = 0.01) after restimulation. In PBMCs from young rats, but not aged rats, preconditioning with low-dose LPS and subsequent stimulation with high-dose LPS resulted in markedly decreased IRAK-1 protein (P = 0.02) and decreased mRNA for IRAK-1 (P < 0.05). In contrast, PBMCs from aged rats treated in this manner continued to express measurable levels of IRAK-1 protein. Preconditioning with low-dose LPS caused an increase in both IRAK-M protein and mRNA (P = 0.05) after stimulation with high-dose LPS only in cells from young rats. These phenotypic characteristics of PBMCs from aged rats can interfere with their ability to develop tolerance to endotoxin.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Aging
/
Leukocytes, Mononuclear
/
Gene Expression Regulation, Enzymologic
/
Lipopolysaccharides
/
Protein Serine-Threonine Kinases
/
Interleukin-1 Receptor-Associated Kinases
Type of study:
Risk_factors_studies
Limits:
Animals
Language:
En
Journal:
Shock
Journal subject:
ANGIOLOGIA
/
CARDIOLOGIA
Year:
2009
Document type:
Article
Affiliation country:
United States