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

American Journal of Reproductive Immunology - Tập 79 Số 3 - 2018
Christopher L. Dixon1, Lauren Richardson2,1, Samantha Sheller‐Miller3,1, George R. Saade1, Ramkumar Menon1
1Department of Obstetrics and Gynecology, The University of Texas Medical Branch, Galveston, TX, USA
2Department of Cell Biology, The University of Texas Medical Branch, Galveston, TX, USA
3Department of Biochemistry and Molecular Biology, The University of Texas Medical Branch, Galveston, TX, USA

Tóm tắt

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.

Từ khóa


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American Journal of Reproductive Immunology

Tập 79 Số 3

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