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Expression and regulation of c-Jun N-terminal kinase (JNK) in endometrial cells in vivo and in vitro

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Abstract

JNK(c-Jun N-terminal kinase) is one of the main types of mitogen-activated protein kinases. JNK modulates inflammation and apoptosis in response to stress. Our hypothesis is that temporal and spatial changes in JNK activity regulate inflammation in human endometrium and that fluctuation in estrogen and progesterone levels may play a role in JNK activation. Therefore, we aimed to determine total-(t-) and active-(phosphorylated, p-) JNK expression in endometrial tissues in vivo by immunohistochemistry, and in vitro by immunocytochemistry and Western blot analysis. Immunohistochemistry revealed moderate cytoplasmic and nuclear t-JNK immunoreactivity, and mostly nuclear p-JNK immunoreactivity throughout the menstrual cycle and early pregnancy. The highest p- and t-JNK immunoreactivity was detected in late secretory phase (P < 0.05). We observed that endometrial stromal cell (ESC)s showed a significant increase in p-JNK expression following 48 h of estrogen combined with progesterone (E2 + P4) withdrawal from the culture conditions, compared to control and non-withdrawal groups (P < 0.05). Upon treatment with JNK inhibitor SP600125, we observed a significantly decreased interleukin (IL)-8 level (P < 0.05) in the presence and absence of E2. These results demonstrate that JNK expression increases during the late secretory phase when the inflammatory response is highest. Inhibition of IL-8 expression by SP600125 suggests that JNK is involved in regulation of proinflammatory mediators of endometrium.

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Authors and Affiliations

  1. Department of Obstetrics, Gynecology and Reproductive Sciences, Section of Reproductive Endocrinology and Infertility, Yale University School of Medicine, New Haven, CT, 06520-8063, USA

    Gulnur Kizilay, Hakan Cakmak, Chih-Feng Yen, Cem Atabekoglu, Aydin Arici & Umit Ali Kayisli

  2. Department of Histology and Embryology, Trakya University Medical Faculty, 22030 , Edirne, Turkey

    Gulnur Kizilay

  3. Department of Obstetrics and Gynecology, Chang Gung Memorial Hospital and Graduate Institute of Clinical Medical Sciences, Chang Gung University College of Medicine, Tao-Yuan, Taiwan

    Chih-Feng Yen

Authors
  1. Gulnur Kizilay
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  2. Hakan Cakmak
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  3. Chih-Feng Yen
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  4. Cem Atabekoglu
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  5. Aydin Arici
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  6. Umit Ali Kayisli
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Correspondence to Umit Ali Kayisli.

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Kizilay, G., Cakmak, H., Yen, CF. et al. Expression and regulation of c-Jun N-terminal kinase (JNK) in endometrial cells in vivo and in vitro. Histochem Cell Biol 130, 761–771 (2008). https://doi.org/10.1007/s00418-008-0421-z

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  • DOI: https://doi.org/10.1007/s00418-008-0421-z

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