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Reproductive Biology and Endocrinology
Published in: Reproductive Biology and Endocrinology 1/2009

Open Access 01-12-2009 | Research

MyD88 and TRIF mediate the cyclic adenosine monophosphate (cAMP) induced corticotropin releasing hormone (CRH) expression in JEG3 choriocarcinoma cell line

Authors: Andy Uh, Charles F Simmons, Catherine Bresee, Nasif Khoury, Adrian F Gombart, Richard C Nicholson, Hande Kocak, Ozlem Equils

Published in: Reproductive Biology and Endocrinology | Issue 1/2009

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Abstract

Background

Classically protein kinase A (PKA) and transcription factor activator protein 1 (AP-1) mediate the cyclic AMP (cAMP) induced-corticotrophin releasing hormone (CRH) expression in the placenta. However enteric Gram (-) bacterial cell wall component lipopolysaccharide (LPS) may also induce-CRH expression via Toll like receptor (TLR)4 and its adaptor molecule Myd88. Here we investigated the role of MyD88, TRIF and IRAK2 on cAMP-induced CRH promoter activation in JEG3 cells in the absence of LPS/TLR4 stimulation.

Methods

JEG3 cells were transfected with CRH-luciferase and Beta-galactosidase expression vectors and either empty or dominant-negative (DN)-MyD88, DN-TRIF or DN-IRAK2 vectors using Fugene6 (Roche). cAMP-induced CRH promoter activation was examined by using a luminometer and luciferase assay. Calorimetric Beta-galactosidase assays were performed to correct for transfection efficiency. Luciferase expression vectors of cAMP-downstream molecules, CRE and AP-1, were used to further examine the signaling cascades.

Results

cAMP stimulation induced AP-1 and CRE promoter expression and led to dose-dependent CRH promoter activation in JEG3 cells. Inhibition of MyD88 signaling blocked cAMP-induced CRE and CRH promoter activation. Inhibition of TRIF signaling blocked cAMP-induced CRH but not CRE expression, while inhibition of IRAK2 did not have an effect on cAMP-induced CRH expression.

Conclusion

MyD88 and TRIF exert direct regulatory effect on cAMP-induced CRH promoter activation in JEG3 cells in the absence of infection. MyD88 most likely interacts with molecules upstream of IRAK2 to regulate cAMP-induced CRH expression.
Appendix
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Metadata
Title
MyD88 and TRIF mediate the cyclic adenosine monophosphate (cAMP) induced corticotropin releasing hormone (CRH) expression in JEG3 choriocarcinoma cell line
Authors
Andy Uh
Charles F Simmons
Catherine Bresee
Nasif Khoury
Adrian F Gombart
Richard C Nicholson
Hande Kocak
Ozlem Equils
Publication date
01-12-2009
Publisher
BioMed Central
Published in
Reproductive Biology and Endocrinology / Issue 1/2009
Electronic ISSN: 1477-7827
DOI
https://doi.org/10.1186/1477-7827-7-74

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