Please use this identifier to cite or link to this item: https://doi.org/10.1038/s41419-018-0327-1
Title: The pro-inflammatory phenotype of the human non-classical monocyte subset is attributed to senescence article
Authors: Ong, S.-M
Hadadi, E
Dang, T.-M
Yeap, W.-H
Tan, C.T.-Y
Ng, T.-P 
Larbi, A
Wong, S.-C 
Keywords: CD14 antigen
CD16 antigen
immunoglobulin enhancer binding protein
interleukin 1alpha
interleukin 1beta
interleukin 6
interleukin 8
Ki 67 antigen
macrophage inflammatory protein 1alpha
macrophage inflammatory protein 1beta
matrix metalloproteinase
microRNA 146a
mitogen activated protein kinase
RANTES
reactive oxygen metabolite
synaptotagmin I
toll like receptor
tumor necrosis factor
adult
antigen expression
Article
atherosclerosis
blood level
cell aging
cell proliferation
cytokine production
gene expression
human
human cell
in vitro study
inflammation
mitochondrial membrane potential
monocyte
osteoarthritis
peripheral blood mononuclear cell
phenotype
priority journal
stimulus response
telomere length
Issue Date: 2018
Publisher: Nature Publishing Group
Citation: Ong, S.-M, Hadadi, E, Dang, T.-M, Yeap, W.-H, Tan, C.T.-Y, Ng, T.-P, Larbi, A, Wong, S.-C (2018). The pro-inflammatory phenotype of the human non-classical monocyte subset is attributed to senescence article. Cell Death and Disease 9 (3) : 266. ScholarBank@NUS Repository. https://doi.org/10.1038/s41419-018-0327-1
Rights: Attribution 4.0 International
Abstract: Human primary monocytes comprise a heterogeneous population that can be classified into three subsets based on CD14 and CD16 expression: classical (CD14high/CD16-), intermediate (CD14high/CD16+), and non-classical (CD14low/CD16+). The non-classical monocytes are the most pro-inflammatory in response to TLR stimulation in vitro, yet they express a remarkably high basal level of miR-146a, a microRNA known to negatively regulate the TLR pathway. This concurrence of a pro-inflammatory status and a high miR-146a level has been associated with cellular senescence in other cell types. Hence, we assessed the three monocyte subsets for evidence of senescence, including proliferative status, telomere length, cellular ROS levels, and mitochondrial membrane potential. Indeed, the non-classical subset exhibited the clearest hallmarks of senescence, followed by the intermediate and then the classical subset. In addition, the non-classical subset secreted pro-inflammatory cytokines basally in vitro. The highly pro-inflammatory nature of the non-classical monocytes could be a manifestation of the senescence-associated secretory phenotype (SASP), likely induced by a high basal NF-?B activity and IL-1? production. Finally, we observed an accumulation of the non-classical monocytes, in conjunction with higher levels of plasma TNF-? and IL-8, in the elderly. These factors may contribute to inflamm-aging and age-related inflammatory conditions, such as atherosclerosis and osteoarthritis. With our new understanding that the non-classical monocyte subset is a senescent population, we can now re-examine the role of this subset in disease conditions where this subset expands. © 2018 The Author(s).
Source Title: Cell Death and Disease
URI: https://scholarbank.nus.edu.sg/handle/10635/178538
ISSN: 2041-4889
DOI: 10.1038/s41419-018-0327-1
Rights: Attribution 4.0 International
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