Expression and regulation of c-Jun N-terminal kinase (JNK) in endometrial cells in vivo and in vitro.
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 (E(2) + P(4)) 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 E(2). 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.
Kizilay
Gulnur
G
Department of Obstetrics, Gynecology and Reproductive Sciences, Section of Reproductive Endocrinology and Infertility, Yale University School of Medicine, New Haven, CT 06520-8063, USA. gulnurk13@gmail.com
Cakmak
Hakan
H
Yen
Chih-Feng
CF
Atabekoglu
Cem
C
Arici
Aydin
A
Kayisli
Umit Ali
UA
D000328:Adult; D000873:Anthracenes / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004717:Endometrium / Q000166:cytology / Q000201:enzymology* / Q000378:metabolism; D004967:Estrogens / Q000494:pharmacology; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D016209:Interleukin-8 / Q000032:analysis / Q000096:biosynthesis / Q000187:drug effects; D048031:JNK Mitogen-Activated Protein Kinases / Q000096:biosynthesis* / Q000187:drug effects / Q000378:metabolism*; D010766:Phosphorylation; D011374:Progesterone / Q000494:pharmacology
D000873:Anthracenes; D004967:Estrogens; D016209:Interleukin-8; C432165:pyrazolanthrone; D011374:Progesterone; D048031:JNK Mitogen-Activated Protein Kinases