Age-associated elevation in TLR5 leads to increased inflammatory responses in the elderly

Feng Qian; Xiaomei Wang; Lin Zhang; Shu Chen; Marta Piecychna; Heather Allore; Linda Bockenstedt; Stephen Malawista; Richard Bucala; Albert C Shaw; Erol Fikrig; Ruth R Montgomery

doi:10.1111/j.1474-9726.2011.00759.x

Age-associated elevation in TLR5 leads to increased inflammatory responses in the elderly

Aging Cell. 2012 Feb;11(1):104-10. doi: 10.1111/j.1474-9726.2011.00759.x. Epub 2011 Nov 28.

Authors

Feng Qian¹, Xiaomei Wang, Lin Zhang, Shu Chen, Marta Piecychna, Heather Allore, Linda Bockenstedt, Stephen Malawista, Richard Bucala, Albert C Shaw, Erol Fikrig, Ruth R Montgomery

Affiliation

¹ Section of Rheumatology, Department of Internal Medicine, Yale University School of Medicine, New Haven, CT 06520-8031, USA.

Abstract

Aging is accompanied by a progressive decline in immune function. Studies have shown age-related decreases in the expression and signaling efficiency of Toll-like receptors (TLRs) in monocytes and dendritic cells and dysregulation of macrophage TLR3. Using a multivariable mixed effect model, we report a highly significant increase in TLR5-induced production of IL-8 from monocytes of older individuals (P < 0.0001). Elevated IL-8 is accompanied by increased expression of TLR5, both protein and mRNA, and by increased levels of TLR5-mediated phosphorylation of MAPK p38 and ERK. We noted incomplete activation of NF-κB in response to TLR5 signaling in monocytes of elderly donors, as reflected by the absence of an associated increase in the production of TNF-α. Elevated TLR5 may provide a critical mechanism to enhance immune responsiveness in older individuals.

Publication types

Research Support, N.I.H., Extramural

MeSH terms

Adult
Aged
Aged, 80 and over
Aging / immunology
Aging / metabolism*
Extracellular Signal-Regulated MAP Kinases / immunology
Extracellular Signal-Regulated MAP Kinases / metabolism
Female
Humans
Inflammation / immunology
Inflammation / metabolism*
Interleukin-8 / biosynthesis
Interleukin-8 / immunology
Male
Middle Aged
Monocytes / immunology
Monocytes / metabolism*
Multivariate Analysis
NF-kappa B / immunology
NF-kappa B / metabolism
Phosphorylation
Protein Transport
RNA, Messenger / biosynthesis*
Signal Transduction / immunology
Toll-Like Receptor 5 / immunology*
Tumor Necrosis Factor-alpha / biosynthesis
Tumor Necrosis Factor-alpha / immunology
p38 Mitogen-Activated Protein Kinases / immunology
p38 Mitogen-Activated Protein Kinases / metabolism

Substances

Interleukin-8
NF-kappa B
RNA, Messenger
TLR5 protein, human
Toll-Like Receptor 5
Tumor Necrosis Factor-alpha
Extracellular Signal-Regulated MAP Kinases
p38 Mitogen-Activated Protein Kinases

Abstract

Publication types

MeSH terms

Substances

Grants and funding