Expression and Activity of Toll-Like Receptors 1–9 in the Human Term Placenta and Changes Associated with Labor at Term

Abstract

Inflammatory processes are involved in the initiation and maintenance of labor, suggesting that Toll-like receptor (TLR) activity within gestation-associated tissues, such as the placenta, might contribute to the process of parturition. Expression of transcripts for TLR1-TLR10 was examined in term (>37 wk of gestation) human placentas collected in the absence of labor (elective caesarean sections; ECS; n = 11) and after the completion of labor (normal vaginal delivery; NVD; n = 12). Placental explants were cultured in the presence of agonists for TLR2, TLR3, TLR4, TLR5, TLR7, TLR8, and TLR9, and cytokine production after 24 h was examined. All placentas expressed transcripts for TLR1-TLR10. Reactivity to all agonists except CpG oligonucleotides was observed, indicating that, other than TLR9, all of the receptors studied yielded functional responses. Placental explants prepared from NVD placentas (n = 17) produced significantly more TNFA in response to lipopolysaccharide (TLR4 agonist) and resiquimod (TLR7/8 agonist) than explants from ECS placentas (n = 17). In contrast, gene expression analysis revealed that only transcripts for TLR2 and TLR5 were significantly elevated in association with labor. The human term placenta expresses a variety of functional TLRs, indicating that this family of receptors has an important role in parturition via as yet undetermined cell types and signaling pathways.

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.…”

Congenital toxoplasmosis: candidate host immune genes relevant for vertical transmission and pathogenesis

“…9,11,71,72 TLR2 and TLR4 are expressed on the surface of the syncytiotrophoblast that recognizes microbes and produces TNF-a, IL-6 and IL-8. 73,74 Intrauterine infections may result in either trophoblast apoptosis or cytokine production that signal immune cells and promote trophoblast survival and destruction of infectious agents. A polymorphism in the TLR2 gene 16934A is linked to diminished synthesis of TNF-a and IFN-g.…”

Response of corneal epithelial cells toStaphylococcus aureus

“…[18][19][20] However, conflicting data has emerged on the expression of TLR2 by corneal epithelial cells, which may relate to the immune privileged nature of this tissue. 21 Surface display of TLR2 on human corneal-limbal epithelial (HCLE) cell surfaces was indirectly inferred through pull-down experiments, and corneal epithelial cells were observed to respond to S. aureus cells and cell products in what was interpreted to be a TLR2-dependent manner.…”