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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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