American Journal of Obstetrics & Gynecology
Volume 199, Issue 3 , Pages 317.e1-317.e6, September 2008

Lipopolysaccharide stimulation of trophoblasts induces corticotropin-releasing hormone expression through MyD88

Presented at the 28th annual meeting of the Society for Maternal–Fetal Medicine, Dallas, TX, Jan. 28-Feb. 2, 2008.

  • Andy Uh, BSc

      Affiliations

    • Division of Pediatric Infectious Diseases, Cedars-Sinai Medical Center, Los Angeles, CA
    • Ahmanson Department of Pediatrics, Steven Spielberg Pediatric Research Center, Burns and Allen Research Institute, Cedars-Sinai Medical Center, Los Angeles, CA
    • David Geffen School of Medicine at UCLA, Cedars-Sinai Medical Center, Los Angeles, CA
    • ,
  • Richard C. Nicholson, BSc, PhD

      Affiliations

    • Mothers and Babies Research Center, Hunter Medical Research Institute, John Hunter Hospital, Newcastle, NSW, Australia
    • ,
  • Gustavo V. Gonzalez, MD

      Affiliations

    • Department of Obstetrics and Gynecology, Cedars-Sinai Medical Center, Los Angeles, CA
    • ,
  • Charles F. Simmons, MD

      Affiliations

    • Ahmanson Department of Pediatrics, Steven Spielberg Pediatric Research Center, Burns and Allen Research Institute, Cedars-Sinai Medical Center, Los Angeles, CA
    • David Geffen School of Medicine at UCLA, Cedars-Sinai Medical Center, Los Angeles, CA
    • ,
  • Adrian Gombart, PhD

      Affiliations

    • David Geffen School of Medicine at UCLA, Cedars-Sinai Medical Center, Los Angeles, CA
    • Department of Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, CA
    • ,
  • Roger Smith, MD, PhD

      Affiliations

    • Mothers and Babies Research Center, Hunter Medical Research Institute, John Hunter Hospital, Newcastle, NSW, Australia
    • ,
  • Ozlem Equils, MD

      Affiliations

    • Division of Pediatric Infectious Diseases, Cedars-Sinai Medical Center, Los Angeles, CA
    • Ahmanson Department of Pediatrics, Steven Spielberg Pediatric Research Center, Burns and Allen Research Institute, Cedars-Sinai Medical Center, Los Angeles, CA
    • David Geffen School of Medicine at UCLA, Cedars-Sinai Medical Center, Los Angeles, CA
    • Corresponding Author InformationReprints: Ozlem Equils, MD, Department of Pediatrics, Cedars-Sinai Medical Center, 8700 Beverly Blvd, Room 4220, Los Angeles, CA 90048

Received 28 February 2008; accepted 27 June 2008.

Objective

We hypothesized that intrauterine infection may lead to placental corticotrophin-releasing hormone (CRH) expression via Toll-like receptor signaling.

Study Design

To test this hypothesis JEG3 cells were stimulated with lipopolysaccharide (LPS), chlamydial heat shock protein 60, and interleukin (IL)-1. CRH expression was assessed by reverse transcription polymerase chain reaction (RT-PCR). The signaling mechanisms that were involved were examined in transient transfection experiments with β-galactosidase, CRH-luciferase, cyclic adenosine monophosphate (AMP) response element–luciferase, dominant-negative (DN)–myeloid differentiation primary response gene (MyD88) and DN-toll-IL-1-receptor domain containing adapter inducing interferon (TRIF) vectors. Luciferase activity was determined by luciferase assay. β-galactosidase assay was performed to determine transfection efficiency.

Results

LPS, chlamydial heat shock protein 60, and IL-1 stimulation led to CRH expression in the JEG3 cells. LPS-induced CRH expression was not due to the autocrine effect of LPS-induced IL-1 because the supernatant from LPS-conditioned JEG3 cells did not induce CRH expression in the naïve cells. DN-MyD88, but not DN-TRIF, blocked the LPS-induced CRH expression. The cAMP response element did not play a role in LPS-induced CRH expression.

Conclusion

Toll-like receptor signaling 4 may induce placental CRH expression through MyD88.

Key words: LPS, MyD88, placenta, pregnancy, preterm delivery, signaling, Toll-like receptors, TRIF, trophoblast

To access this article, please choose from the options below

Login to an existing account or Register a new account.

  • Purchase this article for 30.00 USD (You must login/register to purchase this article)

    Online access for 24 hours. The PDF version can be downloaded as your permanent record.

  • Subscribe to this title

    Get unlimited online access to this article and all other articles in this title 24/7 for one year.

  • Claim access now

    For current subscribers with Society Membership or Account Number.

  • Visit SciVerse ScienceDirect to see if you have access via your institution.
 

 Cite this article as: Uh A, Nicholson RC, Gonzalez GV, et al. Lipopolysaccharide stimulation of trophoblasts induces corticotropin-releasing hormone expression through MyD88. Am J Obstet Gynecol 2008;199:317.e1-317.e6.

 This work was supported by NIH NCRR GCRC Grant M01-RR00425 (O.E.) and March of Dimes Grant 6-FY06-329 (O.E. and R.S.).

PII: S0002-9378(08)00746-1

doi:10.1016/j.ajog.2008.06.091

American Journal of Obstetrics & Gynecology
Volume 199, Issue 3 , Pages 317.e1-317.e6, September 2008

Article Tools

* Image Usage & Resolution