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

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

Research output: Contribution to journalArticlepeer-review

34 Scopus citations

Abstract

Problem: 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. Method of study: 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. Results: 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. Conclusion: 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.

Original languageEnglish (US)
Article numbere12790
JournalAmerican Journal of Reproductive Immunology
Volume79
Issue number3
DOIs
StatePublished - Mar 2018

Keywords

  • fetal membranes
  • interleukin-6
  • lipopolysaccharide
  • p38MAPK
  • tumour necrosis factor-alpha

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Reproductive Medicine
  • Obstetrics and Gynecology

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