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

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

doi:10.1016/j.ajog.2005.07.076

Cited by 141 publications

(147 citation statements)

References 18 publications

Supporting

Mentioning

136

Contrasting

Unclassified

Order By: Relevance

“…This finding was corroborated in a study by Zhu et al, with further evidence revealing increased levels of HMGB1 and RAGE in the placenta of women with severe PE, especially in the cytoplasmic compartment of trophoblasts (Zhu et al 2015). Additionally, RAGE and TLR4, two receptors with affinity for HMGB1, were found to have higher expression in placentas from pregnancies complicated with PE (Kim et al 2005, Chekir et al 2006. Pro-inflammatory effects of HMGB1 via TLR9 have been suggested to contribute to the pathophysiology of PE (Scharfe-Nugent et al 2012).…”

Section: Hmgb1supporting

confidence: 75%

Sterile inflammation and pregnancy complications: a review

Nadeau-Vallée¹,

Obari²,

Palacios³

et al. 2016

Reproduction

219

161

View full text Add to dashboard Cite

Inflammation is essential for successful embryo implantation, pregnancy maintenance and delivery. In the last decade, important advances have been made in regard to endogenous, and therefore non-infectious, initiators of inflammation, which can act through the same receptors as pathogens. These molecules are referred to as damage-associated molecular patterns (DAMPs), and their involvement in reproduction has only recently been unraveled. Even though inflammation is necessary for successful reproduction, untimely activation of inflammatory processes can have devastating effect on pregnancy outcomes. Many DAMPs, such as uric acid, high-mobility group box 1 (HMGB1), interleukin (IL)-1 and cell-free fetal DNA, have been associated with pregnancy complications, such as miscarriages, preeclampsia and preterm birth in preclinical models and in humans. However, the specific contribution of alarmins to these conditions is still under debate, as currently there is lack of information on their mechanism of action. In this review, we discuss the role of sterile inflammation in reproduction, including early implantation and pregnancy complications. Particularly, we focus on major alarmins vastly implicated in numerous sterile inflammatory processes, such as uric acid, HMGB1, IL-1α and cell-free DNA (especially that of fetal origin) while giving an overview of the potential role of other candidate alarmins.Reproduction (2016) 152 R277-R292

show abstract

Section: Hmgb1supporting

confidence: 75%

Sterile inflammation and pregnancy complications: a review

Nadeau-Vallée¹,

Obari²,

Palacios³

et al. 2016

Reproduction

219

161

View full text Add to dashboard Cite

show abstract

“…In addition, we showed that TLR-4 expression is induced in extravillous interstitial trophoblasts in the placental bed of women with preeclampsia [31]. Another group demonstrated increased TLR-4 expression in Hofbauer cells in pregnancies with chorioamnionitis [5], supporting a role for TLRs in this complication of pregnancy.…”

Section: Discussionmentioning

confidence: 74%

Cell Type-specific Expression and Function of Toll-like Receptors 2 and 4 in Human Placenta: Implications in Fetal Infection

Krikun

Abrahams

et al. 2007

Placenta

View full text Add to dashboard Cite

Placental infection is associated with adverse fetal outcomes. Toll-like receptors (TLRs) are critical regulators of the innate immune response based on their ability to recognize and respond to pathogenassociated molecular patterns expressed by microbes. To date, cell-type specific expression and regulation of TLR function in human term placenta remains largely unelucidated. The goal of the current study was to examine the in vivo and in vitro patterns of TLR expression and function in major cell types of term placenta.Immunohistochemical analysis of terminal and stem villi localized TLR-2, which recognizes peptidoglycan (PG) from Gram-positive bacteria, to endothelial cells and macrophages, and to a lesser extent to syncytiotrophoblast (SCTs) and fibroblasts (FIBs). Staining for TLR-4, the receptor for Gram-negative bacterial lipopolysaccharide (LPS), was most prominent in SCTs and endothelial cells. Results from Western blotting, conventional, and quantitative PCR (qRTPCR) analyses using protein and mRNA isolated from cultures of SCTs and myofibroblasts (mFIBs) revealed that SCTs expressed TLR-2 and TLR-4, whereas mFIBs expressed only TLR-4. In addition, qRTPCR showed that LPS treatment increased TLR-2 expression in SCTs, indicating that infection with Gramnegative bacteria may enhance innate immune responses in placenta toward a broad range of microorganisms. In addition, treatment with LPS increased IL-8 levels in both SCTs and mFIBs, whereas PG treatment only stimulated IL-8 levels in SCTs. Our results indicate that there exist cell type-specific patterns of TLR function in placenta which likely regulate innate immune response at the maternal-fetal interface.

show abstract

“…TLR4 protein expression was found to be increased in interstitial trophoblasts at the placental bed of patients with preeclampsia. The authors hypothesized that danger signals (host or microbial in nature) at the feto-maternal interface, which are recognized by trophoblasts through TLR4, may play a key role in creating a local abnormal cytokine milieu leading to the development of preeclampsia (44). As trophoblast cells are fetal in origin, this finding raises the possibility that fetal instead of maternal TLR4 gene polymorphisms influence the risk of preeclampsia.…”

Section: Discussionmentioning

confidence: 78%