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An additive interaction between the NFkappaB and estrogen receptor signalling pathways in human endometrial epithelial cells.

King AE, Collins F, Klonisch T, Sallenave JM, Critchley HO, Saunders PT - Hum. Reprod. (2009)

Bottom Line: Real-time PCR showed that mRNA for the p65 and p105 NFkappaB subunits is maximally expressed in endometrium from the putative implantation window.This is a gene-dependent action as there is no additive effect on cyclin D1 or progesterone receptor expression.In summary, we have established that NFkappaB signalling proteins are expressed in normal endometrium and report that IL-1beta can enhance the actions of E2 in a cell line derived from healthy endometrium.

View Article: PubMed Central - PubMed

Affiliation: Reproductive & Developmental Sciences, University of Edinburgh, Edinburgh, UK.

ABSTRACT

Background: Human embryo implantation is regulated by estradiol (E2), progesterone and locally produced mediators including interleukin-1beta (IL-1beta). Interactions between the estrogen receptor (ER) and NF kappa B (NFkappaB) signalling pathways have been reported in other systems but have not been detailed in human endometrium.

Methods and results: Real-time PCR showed that mRNA for the p65 and p105 NFkappaB subunits is maximally expressed in endometrium from the putative implantation window. Both subunits are localized in the endometrial epithelium throughout the menstrual cycle. Reporter assays for estrogen response element (ERE) activity were used to examine functional interactions between ER and NFkappaB in telomerase immortalized endometrial epithelial cells (TERT-EEC). E2 and IL-1beta treatment of TERT-EECs enhances ERE activity by a NFkappaB and ER dependent mechanism; this effect could be mediated by ERalpha or ERbeta. E2 and IL-1beta also positively interact to increase endogenous gene expression of prostaglandin E synthase and c-myc. This is a gene-dependent action as there is no additive effect on cyclin D1 or progesterone receptor expression.

Conclusion: In summary, we have established that NFkappaB signalling proteins are expressed in normal endometrium and report that IL-1beta can enhance the actions of E2 in a cell line derived from healthy endometrium. This mechanism may allow IL-1beta, possibly from the developing embryo, to modulate the function of the endometrial epithelium to promote successful implantation, for example by regulating prostaglandin production. Aberrations in the interaction between the ER and NFkappaB signalling pathways may have a negative impact on implantation contributing to pathologies such as early pregnancy loss and infertility.

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Related in: MedlinePlus

E2 and IL-1β positively interact to enhance estrogen response element (ERE) activity in an estrogen receptor (ER) dependent manner in TERT-EECs.
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DEP421F3: E2 and IL-1β positively interact to enhance estrogen response element (ERE) activity in an estrogen receptor (ER) dependent manner in TERT-EECs.

Mentions: Incubation of TERT-EECs with 10−8M E2 resulted in a 5-fold increase in the ERE-dependent expression of luciferase (Fig. 3). In contrast with the Ishikawa cells, increased expression was also observed when cells were treated with IL-1β alone and simultaneous exposure to E2 and IL-1β increased ERE-luciferase reporter activity 15-fold (Fig. 3; P < 0.01). Both basal ERE activity and the increased ERE activity that occurred when TERT-EEC were treated with E2, IL-1β or E2 + IL-1β were abolished by the presence of the ER antagonist, ICI 182720.


An additive interaction between the NFkappaB and estrogen receptor signalling pathways in human endometrial epithelial cells.

King AE, Collins F, Klonisch T, Sallenave JM, Critchley HO, Saunders PT - Hum. Reprod. (2009)

E2 and IL-1β positively interact to enhance estrogen response element (ERE) activity in an estrogen receptor (ER) dependent manner in TERT-EECs.
© Copyright Policy - creative-commons
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC2806182&req=5

DEP421F3: E2 and IL-1β positively interact to enhance estrogen response element (ERE) activity in an estrogen receptor (ER) dependent manner in TERT-EECs.
Mentions: Incubation of TERT-EECs with 10−8M E2 resulted in a 5-fold increase in the ERE-dependent expression of luciferase (Fig. 3). In contrast with the Ishikawa cells, increased expression was also observed when cells were treated with IL-1β alone and simultaneous exposure to E2 and IL-1β increased ERE-luciferase reporter activity 15-fold (Fig. 3; P < 0.01). Both basal ERE activity and the increased ERE activity that occurred when TERT-EEC were treated with E2, IL-1β or E2 + IL-1β were abolished by the presence of the ER antagonist, ICI 182720.

Bottom Line: Real-time PCR showed that mRNA for the p65 and p105 NFkappaB subunits is maximally expressed in endometrium from the putative implantation window.This is a gene-dependent action as there is no additive effect on cyclin D1 or progesterone receptor expression.In summary, we have established that NFkappaB signalling proteins are expressed in normal endometrium and report that IL-1beta can enhance the actions of E2 in a cell line derived from healthy endometrium.

View Article: PubMed Central - PubMed

Affiliation: Reproductive & Developmental Sciences, University of Edinburgh, Edinburgh, UK.

ABSTRACT

Background: Human embryo implantation is regulated by estradiol (E2), progesterone and locally produced mediators including interleukin-1beta (IL-1beta). Interactions between the estrogen receptor (ER) and NF kappa B (NFkappaB) signalling pathways have been reported in other systems but have not been detailed in human endometrium.

Methods and results: Real-time PCR showed that mRNA for the p65 and p105 NFkappaB subunits is maximally expressed in endometrium from the putative implantation window. Both subunits are localized in the endometrial epithelium throughout the menstrual cycle. Reporter assays for estrogen response element (ERE) activity were used to examine functional interactions between ER and NFkappaB in telomerase immortalized endometrial epithelial cells (TERT-EEC). E2 and IL-1beta treatment of TERT-EECs enhances ERE activity by a NFkappaB and ER dependent mechanism; this effect could be mediated by ERalpha or ERbeta. E2 and IL-1beta also positively interact to increase endogenous gene expression of prostaglandin E synthase and c-myc. This is a gene-dependent action as there is no additive effect on cyclin D1 or progesterone receptor expression.

Conclusion: In summary, we have established that NFkappaB signalling proteins are expressed in normal endometrium and report that IL-1beta can enhance the actions of E2 in a cell line derived from healthy endometrium. This mechanism may allow IL-1beta, possibly from the developing embryo, to modulate the function of the endometrial epithelium to promote successful implantation, for example by regulating prostaglandin production. Aberrations in the interaction between the ER and NFkappaB signalling pathways may have a negative impact on implantation contributing to pathologies such as early pregnancy loss and infertility.

Show MeSH
Related in: MedlinePlus