Effects of aging on endotoxin tolerance induced by lipopolysaccharides derived from Porphyromonas gingivalis and Escherichia coli.
BACKGROUND
Periodontitis is a bacterially induced chronic inflammatory disease. Exposure of the host to periodontal pathogens and their virulence factors induces a state of hyporesponsiveness to subsequent stimulations, termed endotoxin tolerance. Aging has a profound effect on immune response to bacteria challenge. The aim of this study was to explore the effects of aging on endotoxin tolerance induced by Porphyromonas gingivalis (P. gingivalis) lipopolysaccharide (LPS) and Escherichia coli (E. coli) LPS in murine peritoneal macrophages.


RESULTS
We studied the cytokine production (TNF-α and IL-10) and Toll-like receptor 2, 4 (TLR2, 4) gene and protein expressions in peritoneal macrophages from young (2-month-old) and middle-aged (12-month-old) ICR mice following single or repeated P. gingivalis LPS or E. coli LPS stimulation. Pretreatment of peritoneal macrophages with P. gingivalis LPS or E. coli LPS resulted in a reduction in TNF-α production and an increase in IL-10 production upon secondary stimulation (p<0.05), and the markedly lower levels of TNF-α and higher levels of IL-10 were observed in macrophages from young mice compared with those from middle-aged mice (p<0.05). In addition, LPS restimulations also led to the significantly lower expression levels of TLR2, 4 mRNA and protein in macrophages from young mice (p<0.05).


CONCLUSIONS
Repeated LPS stimulations triggered endotoxin tolerance in peritoneal macrophages and the ability to develop tolerance in young mice was more excellent. The impaired ability to develop endotoxin tolerance resulted from aging might be related to TLR2, 4 and might lead to the incontrollable periodontal inflammation in older adults.
Institute of Stomatology, Nanjing Medical University, Nanjing, China.
Ying
Y
Sun
Hui
H
Li
Mi-Fang
MF
Yang
Wei
W
Shu
Meng-Jun
MJ
Sun
Yan
Y
Xu
D000375:Aging / Q000276:immunology*; D000818:Animals; D016207:Cytokines / Q000096:biosynthesis / Q000276:immunology; D004731:Endotoxins / Q000276:immunology*; D004926:Escherichia coli / Q000737:chemistry / Q000276:immunology*; D005786:Gene Expression Regulation; D007108:Immune Tolerance / Q000276:immunology*; D008070:Lipopolysaccharides / Q000276:immunology*; D017737:Macrophages, Peritoneal / Q000276:immunology / Q000378:metabolism; D051379:Mice; D010518:Periodontitis / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D016966:Porphyromonas gingivalis / Q000737:chemistry / Q000276:immunology*; D051195:Toll-Like Receptor 2 / Q000235:genetics / Q000378:metabolism; D051197:Toll-Like Receptor 4 / Q000235:genetics / Q000378:metabolism
D016207:Cytokines; D004731:Endotoxins; D008070:Lipopolysaccharides; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4