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A distinct mechanism of senescence activation in amnion epithelial cells by infection, inflammation, and oxidative stress
Author(s) -
Dixon Christopher Luke,
Richardson Lauren,
ShellerMiller Samantha,
Saade George,
Me Ramkumar
Publication year - 2018
Publication title -
american journal of reproductive immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.071
H-Index - 97
eISSN - 1600-0897
pISSN - 1046-7408
DOI - 10.1111/aji.12790
Subject(s) - senescence , mapk/erk pathway , tumor necrosis factor alpha , lipopolysaccharide , inflammation , p38 mitogen activated protein kinases , oxidative stress , amnion , biology , immunology , andrology , endocrinology , medicine , microbiology and biotechnology , fetus , signal transduction , pregnancy , genetics
Problem We investigated p38 MAPK 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 ( AEC s) 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. AEC s were cotreated with the antioxidant N‐acetyl cysteine ( NAC ) and p38 MAPK inhibitor SB 203580 to determine the effect of OS and p38 MAPK . Western blot analysis was performed for active (Phospho‐p38 MAPK ) and total p38 MAPK . Senescence was determined by flow cytometry, and culture supernatants were tested for IL ‐6 using ELISA. Results TNF ‐α, but not LPS , increased p38 MAPK 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 p38 MAPK activation by TNF ‐α. p38 MAPK inhibitor SB 203580 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.