- Title
- MyD88 and TRIF mediate the cyclic adenosine monophosphate (cAMP) induced corticotropin releasing hormone (CRH) expression in JEG3 choriocarcinoma cell line
- Creator
- Uh, Andy; Simmons, Charles F.; Bresee, Catherine; Khoury, Nasif; Gombart, Adrian F.; Nicholson, Richard C.; Kocak, Hande; Equils, Ozlem
- Relation
- Reproductive Biology and Endocrinology Vol. 7, Issue 74
- Publisher Link
- http://dx.doi.org/10.1186/1477-7827-7-74
- Publisher
- BioMed Central
- Resource Type
- journal article
- Date
- 2009
- Description
- 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.
- Subject
- cyclic adenosine monophosphate; MyD88; TRIF; corticotrophin releasing hormones
- Identifier
- http://hdl.handle.net/1959.13/809158
- Identifier
- uon:7838
- Identifier
- ISSN:1477-7827
- Language
- eng
- Full Text
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