Toll-like receptor 4: A potential link between "danger signals," the innate immune system, and preeclampsia?

Mee Kim Yeon, Roberto Romero, Young Oh Seo, Jai Kim Chong, Brian A. Kilburn, D. Randall Armant, Kae Nien Jyh, Ricardo Gomez, Moshe Mazor, Shigeru Saito, Vikki M. Abrahams, Gil Mor

    Research output: Contribution to journalArticlepeer-review

    53 Scopus citations


    Objective: Toll-like receptors (TLRs) recognize microbial ligands and host products that are released during tissue damage, the so-called "danger signals." This study was conducted to determine whether changes in TLR-4 and TLR-2 expressions can be detected in the trophoblasts at the placental bed of women with and without preeclampsia. Study design: Placental bed biopsy specimens were obtained from women with: (1) normal term pregnancies with and without labor (each n = 20); (2) preeclampsia who delivered preterm (n = 15); and (3) preterm labor and intact membranes with and without chorioamnionitis (each n = 15). The expression pattern of TLR-4 and TLR-2 in the trophoblasts was analyzed by double immunohistochemistry. Results: (1) The median percentage of TLR-4 positive interstitial trophoblasts was significantly higher in patients with preeclampsia than in patients with preterm labor without or with histologic chorioamnionitis (P = .0002 and P = .02, respectively). (2) The median percentage of TLR-2 positive interstitial trophoblasts was not different among the study groups (P > .05). (3) TLR-4 positive trophoblasts were also frequently immunoreactive to activated nuclear factor-κB, tumor necrosis factor-α, and M30 (a specific apoptosis antigen for trophoblast). (4) Lipopolysaccharide treatment inhibited the migration of trophoblast cell lines in vitro. Conclusion: TLR-4 protein expression is increased in interstitial trophoblasts of patients with preeclampsia. We propose that "danger signals" at the feto-maternal interface, which are recognized by trophoblasts through TLR-4, may play a key role in the creation of a local abnormal cytokine milieu. This suggests a novel mechanism that links the activation of the innate immune system through TLR-4 and preeclampsia.

    Original languageEnglish
    Pages (from-to)921.e1-921.e8
    JournalAmerican Journal of Obstetrics and Gynecology
    Issue number3 SUPPL.
    StatePublished - 1 Jan 2005


    • Danger signal
    • Innate immunity
    • NF-Kappa B
    • Placental bed biopsy
    • Preeclampsia
    • Pregnancy
    • Toll-like receptor
    • Toll-like receptor-2
    • Toll-like receptor-4
    • Trophoblast migration
    • Tumor necrosis factor-α

    ASJC Scopus subject areas

    • Obstetrics and Gynecology


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