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National Institute of Environmental Health Sciences

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Publication Detail

Title: A distinct mechanism of senescence activation in amnion epithelial cells by infection, inflammation, and oxidative stress.

Authors: Dixon, Christopher Luke; Richardson, Lauren; Sheller-Miller, Samantha; Saade, George; Menon, Ramkumar

Published In Am J Reprod Immunol, (2018 Mar)

Abstract: We investigated p38MAPK activation-induced fetal membrane cell senescence in response to inflammation (tumour necrosis factor-alpha [TNF-α]) and infection (lipopolysaccharide [LPS]), factors associated with spontaneous preterm birth.Primary amnion epithelial cells (AECs) were exposed to TNF-α, 50 ng/mL and LPS, 100 ng/mL. Cigarette smoke extract (CSE), a known OS inducer, was used as positive control. AECs were cotreated with the antioxidant N-acetyl cysteine (NAC) and p38MAPK inhibitor SB203580 to determine the effect of OS and p38MAPK. Western blot analysis was performed for active (Phospho-p38MAPK) and total p38MAPK. Senescence was determined by flow cytometry, and culture supernatants were tested for IL-6 using ELISA.TNF-α, but not LPS, increased p38MAPK activation compared to untreated cells (P = .01). The number of senescent cells and senescence-associated IL-6 was higher in both TNF-α and LPS-treated cells compared to control (P = .001, P = .01, respectively). Antioxidant NAC inhibited p38MAPK activation by TNF-α. p38MAPK inhibitor SB203580 reduced the development of senescence and IL-6 by TNF-α and LPS. CSE treatment validated our current data.TNF-α caused OS-mediated p38MAPK induction, senescence, and IL-6 increase from AECs. LPS also induced senescence and IL-6 increase. Inflammatory and infectious factors may cause premature fetal cell senescence contributing to preterm birth pathophysiology.

PubMed ID: 29193446 Exiting the NIEHS site

MeSH Terms: Amnion/pathology*; Cells, Cultured; Cellular Senescence; Epithelial Cells/immunology*; Extraembryonic Membranes/pathology*; Female; Humans; Imidazoles/pharmacology; Infections/immunology*; Inflammation/immunology*; Interleukin-6/metabolism; Lipopolysaccharides/immunology; Oxidative Stress; Pregnancy; Premature Birth/immunology*; Primary Cell Culture; Pyridines/pharmacology; Tumor Necrosis Factor-alpha/immunology; p38 Mitogen-Activated Protein Kinases/metabolism

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