Evidence for Activation of Toll-Like Receptor and Receptor for Advanced Glycation End Products in Preterm Birth

Abstract

Objective. Individuals with inflammation have a myriad of pregnancy aberrations including increasing their preterm birth risk. Toll-like receptors (TLRs) and receptor for advanced glycation end products (RAGE) and their ligands were all found to play a key role in inflammation. In the present study, we reviewed TLR and RAGE expression, their ligands, and signaling in preterm birth. Research Design and Methods. A systematic search was performed in the electronic databases PubMed and ScienceDirect up to July 2010, combining the keywords “preterm birth,” “TLR”, “RAGE”, “danger signal”, “alarmin”, “genomewide,” “microarray,” and “proteomics” with specific expression profiles of genes and proteins. Results. This paper provides data on TLR and RAGE levels and critical downstream signaling events including NF-kappaB-dependent proinflammatory cytokine expression in preterm birth. About half of the genes and proteins specifically present in preterm birth have the properties of endogenous ligands “alarmin” for receptor activation. The interactions between the TLR-mediated acute inflammation and RAGE-mediated chronic inflammation have clear implications for preterm birth via the TLR and RAGE system, which may be acting collectively. Conclusions. TLR and RAGE expression and their ligands, signaling, and functional activation are increased in preterm birth and may contribute to the proinflammatory state.

Novel Noncompetitive IL-1 Receptor–Biased Ligand Prevents Infection- and Inflammation-Induced Preterm Birth

“…We focused on IL-1 to control. (G) Quantitative PCR of RAW-Blue macrophages treated with IL-1b (1 mg/ml) or vehicle with or without 101.10 (10 26 M) or Kineret (1.5 mg/ml) for and upstream TLR4 and TLR2 (66) pathways proposed by an abundance of literature to be implicated in triggering human PTB (67)(68)(69)(70); also, efficacy of 101.10 was shown in a relevant human cell line. Concordantly, in the current study, several mediators of inflammation were induced in our rodent models (e.g., IL-6, IL-8, and cyclooxygenase-2); yet, specific inhibition of IL-1R by 101.10 reduced PTB induced by every stimulus (IL-1, LPS, LTA) tested, highlighting its critical role.…”

The Effect of Inflammation on Preterm Birth

“…In addition, recent studies demonstrated associations between elevated levels of circulating proinflammatory cytokines, particularly interleukin (IL) 6, IL-1beta, and tumor necrosis factor alpha (TNFalpha) and preterm birth . These inflammatory cytokines might link the pathology of uterine contraction, uterine cervical ripening, and preterm premature rupture of membranes (Noguchi et al, 2010). Stimulation of TLRs with their ligands has been shown to induce proinflammatory cytokine release in uterine epithelial cells, fetal membranes and placenta (Schaefer et al, 2004;Noguchi et al, 2010).…”

“…These inflammatory cytokines might link the pathology of uterine contraction, uterine cervical ripening, and preterm premature rupture of membranes (Noguchi et al, 2010). Stimulation of TLRs with their ligands has been shown to induce proinflammatory cytokine release in uterine epithelial cells, fetal membranes and placenta (Schaefer et al, 2004;Noguchi et al, 2010). Moreover, the presence of TLR4 detected by immunohistochemistry in the amnios of women at labor suggested the possibility that stimulation of TLRs with their ligands induce proinflammatory cytokine release, conducting to labor (Schaefer et al, 2004;Noguchi et al, 2010).…”

The role of systemic inflammatory response syndrome in preterm labour development

“…В целом исследования взаимосвязи между полиморфизмом ге-нов цитокинов, в том числе и наиболее изученного ФНО-α/G308A, риском преждевременных родов дали неоднозначные, и порой противоречивые результаты. Это, возможно, объясняется несколькими факторами: полиморфизмы тесно связаны с другими близлежа-щими функциональными изменениями гена; суще-ствуют ген-взаимодействия, которые определяют кли-нические проявления; этническое разнообразие изу-чаемых групп; иные важные воздействия окружающей среды полностью не учитывались или были исключе-ны при исследовании популяций [32].…”

“…В последние годы появляются работы о роли механизмов врожденного иммунитета в репродук-тивной функции человека [32,33]. В развитии ряда патологических процессов, в том числе воспаления, имеют значение распознающие рецепторы врожден-ной иммунной системы toll-подобные рецепторы (TLRs), они обеспечивают интегрирующую и регу-лирующую роль в активации и реализации врожден-ного иммунного ответа на микробные патогены [33,34].…”