Upregulated ex vivo expression of stress-responsive inflammatory pathway genes by LPS-challenged CD14(+) monocytes in frail older adults.
Frailty has been increasingly recognized as an important clinical syndrome in old age. The frailty syndrome is characterized by chronic inflammation, decreased functional and physiologic reserve, and increased vulnerability to stressors, leading to disability and mortality. However, molecular mechanisms that contribute to inflammation activation and regulation in frail older adults have not been investigated. To begin to address this, we conducted a pathway-specific gene array analysis of 367 inflammatory pathway genes by lipopolysaccharide (LPS)-challenged CD14(+) monocytes from 32 community-dwelling frail and age-, race-, and sex-paired nonfrail older adults (mean age 83 years, range 72-94). The results showed that ex vivo LPS-challenge induced average 2.0-fold or higher upregulated expression of 116 genes in frail participants and 85 genes in paired nonfrail controls. In addition, frail participants had 2-fold or higher upregulation in LPS-induced expression of 7 stress-responsive genes than nonfrail controls with validation by quantitative real time RT-PCR. These findings suggest upregulated expression of specific stress-responsive genes in monocyte-mediated inflammatory pathway in the syndrome of frailty with potential mechanistic and interventional implications.
Qu
Tao
T
Johns Hopkins University School of Medicine, Biology of Frailty Program, Division of Geriatric Medicine & Gerontology, Department of Medicine, Baltimore, MD, USA.
Walston
Jeremy D
JD
Yang
Huanle
H
Fedarko
Neal S
NS
Xue
Qian-Li
QL
Beamer
Brock A
BA
Ferrucci
Luigi
L
Rose
Noel R
NR
Leng
Sean X
SX
D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000235:genetics / Q000276:immunology*; D016022:Case-Control Studies; D002478:Cells, Cultured; D005260:Female; D016330:Frail Elderly; D020869:Gene Expression Profiling / Q000379:methods; D006801:Humans; D007249:Inflammation / Q000235:genetics / Q000276:immunology*; D018836:Inflammation Mediators / Q000378:metabolism*; D018950:Lipopolysaccharide Receptors / Q000032:analysis*; D008070:Lipopolysaccharides / Q000276:immunology*; D008297:Male; D009000:Monocytes / Q000276:immunology*; D020411:Oligonucleotide Array Sequence Analysis; D016133:Polymerase Chain Reaction; D015203:Reproducibility of Results; D013312:Stress, Physiological / Q000235:genetics / Q000276:immunology*; D015854:Up-Regulation
D018836:Inflammation Mediators; D018950:Lipopolysaccharide Receptors; D008070:Lipopolysaccharides