Impact of progesterone on cytokine-stimulated nuclear factor-kappaB signaling in HeLa cells.
OBJECTIVE
A key event in the pathways leading to preterm labor may be the activation of nuclear factor-kappaB (NF-kappaB) in the fetal membranes and the cervix. Anti-inflammatory agents, such as the corticosteroids, inhibit the activation of NF-kappaB. We proposed to investigate the effects of progesterone pretreatment on cytokine-stimulated activation of NF-kappaB in HeLa cells, a human cervical epithelial cell line.


METHODS
HeLa cells were pretreated with 10(-7) M progesterone for 24 hours and exposed to 1 ng/mL interleukin-1beta (IL-1beta) for 1 hour. Nuclear and cytosolic extracts were subjected to Western blot analysis using anti-p65 and anti-inhibitory protein-kappaBalpha (anti-IkappaBalpha) antibodies. Densitometric data (n=5) were compared using Kruskal-Wallis test.


RESULTS
Pretreatment with progesterone interfered with IL-1beta-induced IkappaBalpha degradation. However, progesterone pretreatment resulted in a significant decrease in NF-kappaB protein subunit p65 in the cytoplasm. Pretreatment with progesterone did not reduce the amount of nuclear p65 and did not interfere with nuclear translocation of p65.


CONCLUSIONS
Our observations suggest that any possible role played by progesterone in preterm labor prevention is not exerted through anti-inflammatory mechanisms of NF-kappaB down-regulation.
Vidaeff
Alex C
AC
Department of Obstetrics, Gynecology and Reproductive Sciences, Division of Maternal-Fetal Medicine, University of Texas-Houston Medical School, Houston, TX 77030, USA. alex.c.vidaeff@uth.tmc.edu
Ramin
Susan M
SM
Gilstrap
Larry C
LC
Bishop
Karen D
KD
Alcorn
Joseph L
JL
D006367:HeLa Cells; D006801:Humans; D053583:Interleukin-1beta / Q000494:pharmacology; D016328:NF-kappa B / Q000187:drug effects* / Q000378:metabolism; D047928:Premature Birth / Q000378:metabolism; D011374:Progesterone / Q000494:pharmacology*; D011372:Progestins / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects*; D051996:Transcription Factor RelA / Q000187:drug effects / Q000378:metabolism
D053583:Interleukin-1beta; D016328:NF-kappa B; D011372:Progestins; D051996:Transcription Factor RelA; D011374:Progesterone