From: Long-term cardiovascular complications following sepsis: is senescence the missing link?
Cells | Species of origin | Sepsis model | Analysis time points | Results | References | |||||
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In vitro | ||||||||||
Microglia cells (BV2 cell) | C57BL/6 mouse | 10 ng/ml LPS stimulation: once 3 times: once every 48 h for 4 h each 6 times: once every 24 h for 4 h each | After 1, 6 or 12 days | Kinetics (6–12 days): •Inhibition of cell proliferation •Elevated degree of: − Cell cycle arrest in the G0/G1 phase − The aging associated proteins p53 − Senescence-associated β-galactosidase activity − Senescence-associated heterochromatic foci (SAHF) | [92] | |||||
Type II pulmonary alveolar epithelial cells (A549 immortalized cells) | Human | 5—20 μg/ml LPS single stimulation for 24 h | After 1, 3 or 7 days | •Elevated degree of: − Senescence-associated β-galactosidase activity •No decrease in telomere length | [89] | |||||
Dental pulp stem cells (DPSCs) | Human | 10 ng/ml Escherichia coli LPS (serotype 0111:B4) stimulation: once for 6 h 3 times: once every 48 h for 6 h each 6 times: once every 24 h for 6 h each | After 1 h | Senescence-like morphology •Inhibition of cell proliferation •Elevated degree of: − Cell cycle arrest in the G1 phase − Senescence-associated β-galactosidase activity − The aging associated p16INK4A − of p16INK4A mRNA •Knockdown of p16INK4A expression by siRNA transfection reversed the senescent features of LPS-treated DPSCs | [94] | |||||
Adipocyte progenitors (stromal-vascular cells) | C57BL/6 mouse | 0.2 μg/ml LPS stimulation for 24 h | After 3 days | •Elevated degree of: − p53 phosphorylation − Senescence-associated β-galactosidase activity − β-galactosidase-positive cells − mRNA indicating significant SAPS (TNFα, IL-1β, IL-6, monocyte chemoattractant protein-1 (MCP-1), and VEGFα) •No accelerate telomere shortening | [93] | |||||
Type II pulmonary alveolar epithelial cells (A549 immortalized cells) Human nasopharyngeal cells (HEp-2 immortalized cells) | Human | Human respiratory syncytial virus (Pneumovirus genus of the Paramyxoviridae family) | After 48 h | •Senescence-associated secretory phenotype (SASP) in supernatant •Elevated degree of: − The aging associated proteins p53 − Senescence-associated β-galactosidase activity | [90] | |||||
Neuroblastoma Neuro2a Cells | Mouse | H7N9 Influenza A Virus | After 3 days | •Senescent cell-like morphology •Increase senescence-associated β-galactosidase activity | [91] | |||||
In vivo | ||||||||||
Blood, spleen and kidney samples (unspecified cell type) | Young male BALB/c mice | 15 mg/kg LPS intraperitoneal injection | After 1 h or 48 h | •Dose-dependent telomere shortening in the spleen and liver at 48 h (but not at 1 h) measured by quantitative polymerase chain reaction (PCR) •No difference in telomerase expression in kidney homogenates 1 h after LPS | [95] | |||||
Lung tissue (unspecified cell type) | Young male C57BL/6 mice | Two-hit mouse model using CLP followed by sublethal Pseudomonas aeruginosa lung infection 4 h later | 24 h after Pseudomonas aeruginosa lung infection | •Upregulation of: − Senescence-associated biomarker p16ink4a − Senescence-associated β-galactosidase activity | [96] | |||||
Vascular tissue | Young Wistar male rats | CLP | 3, 7 or 90 days after CLP | •Upregulation of: − The aging associated proteins p53, p21 and p16 − The aging associated proteins p53 localized in the endothelium | [34] |