Placental TLR/NLR expression signatures are altered with gestational age and inflammation

Kumar, Navin; Nandula, Padma; Menden, Heather; Jarzembowski, Jason A.; Sampath, Venkatesh

doi:10.1080/14767058.2016.1214705

Cited by 12 publications

(10 citation statements)

References 32 publications

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“…A most recent study reported that TLR5 mRNA expression was increased in placenta with chorioamnionitis. ( 12 ) Moreover, the present study demonstrated that TLR5 protein expression was increased and showed a trend toward an increase, in the amnion and chorion respectively, i.e., the fetal membrane, and not affected in the decidua and villi with preterm HCA. The stimulation by TLR5 agonist also caused IL-6 production in the fetal membrane, as well as TLR1/2, TLR4, and TLR2/6 agonists, which is consistent with the previous reports.…”

Section: Discussionsupporting

confidence: 56%

“…( 9 – 11 ) In addition, it was reported that TLR5 mRNA expression among the members of TLR family is only increased in the placenta with chorioamnionitis, although the samples were collected from mixed term and preterm subjects. ( 12 ) However, these findings are partial evidence, thus, additional work is needed to confirm if TLR5 is involved in chorioamnionitis pathology.…”

Section: Introductionmentioning

confidence: 99%

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The expression of Toll-like receptor 5 in preterm histologic chorioamnionitis

Moroi

Kotani

Miki

et al. 2018

J. Clin. Biochem. Nutr.

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Spontaneous preterm birth is often caused by chorioamnionitis. Toll-like receptors (TLRs) have a role in the response of the innate immune system. The role of TLR5 in chorioamnionitis remains unclear: however, TLR5 was reported to have a significantly stronger effect on the induction of interleukin (IL)-6 when compared with other TLRs in amniotic epithelial cells. The aim of this study was to investigate TLR5 expression in placentas with preterm histologic chorioamnionitis (HCA). The expression levels of TLR5 were evaluated in the amnions, chorions, deciduae and villi with and without HCA using immunohistochemistry. The co-localization of IL-6 or IL-8 with TLR5 was examined by immunofluorescence. The production of IL-6 was examined in primary tissue cultured fetal membranes treated with and without the TLR5 agonist. The protein expression of TLR5 was significantly increased in amnions with HCA (p<0.05) and showed a trend toward an increase in chorions with HCA, whereas no significant difference was detected in the villi and decidua. TLR5 co-localized with IL-6 and IL-8 in amnions and chorions. IL-6 showed a significant increase (p<0.05) with the TLR5 agonist. These results suggest that TLR5 plays a role in the pathogenesis of preterm HCA and IL-6 production.

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Section: Discussionsupporting

confidence: 56%

Section: Introductionmentioning

confidence: 99%

The expression of Toll-like receptor 5 in preterm histologic chorioamnionitis

Moroi

Kotani

Miki

et al. 2018

J. Clin. Biochem. Nutr.

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“…taneous PTB (63). The Tlr4/nF-κB pathway also plays a critical role in inflammation, and reports have confirmed that the expression and activation of Tlr4/nF-κB signaling are involved in gestational inflammation (64). In the present study, the role of HMGB1, its downstream Tlr4/nF-κB signaling in preterm cervical epithelial inflammation and its upstream regulatory mechanism were explored.…”

Section: Discussionmentioning

confidence: 75%

“…upregulating the expression of cytokines and other inflammatory mediators (17)(18)(19)(20). a previous study has revealed that the TLR4/NF-кB signaling pathway is involved in advancing gestational age, exposure to chorioamnionitis and preterm premature rupture of membranes (PProM) (21). However, the regulatory mechanism of HMGB1 and Tlr4/nF-κB signaling in inflammatory activation in PTB remains unknown.…”

Section: Mir-199a-3p Suppresses Cervical Epithelial Cell Inflammationmentioning

confidence: 99%

miR‑199a‑3p suppresses cervical epithelial cell inflammation by inhibiting the HMGB1/TLR4/NF‑κB pathway in preterm birth

et al. 2020

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Preterm birth (PTB) is the primary cause of neonatal mortality worldwide. Infection and inflammation are considered to be the primary causes of PTB. cervical remodeling is an important step in the process of preterm delivery, and the destruction of the cervical epithelial barrier and inflammation are important triggers of cervical remodeling. The aim of the present study was to determine the effect and underlying mechanism of microrna (mir)-199a-3p/high-mobility group box 1 protein (HMGB1) signaling in cervical epithelial inflammation in PTB. The results of this study revealed that miR-199a-3p was significantly decreased in cervical epithelial tissue samples from patients in both the preterm labor and preterm premature rupture of membrane groups. This decrease was also observed in tissue samples from a lipopolysaccharide (lPS)-induced PTB mouse model and in lPS-induced ectocervical and endocervical cells. Whereas, the expression of HMGB1 and toll-like receptor 4 (TLR4) was significantly increased, which was associated with the upregulation of interleukin (il)-1β and tumor necrosis factor (TnF)-α expression. Furthermore, overexpression of mir-199a-3p significantly suppressed the expression and activation of HMGB1 and Tlr4/nF-κB signaling, and decreased the levels of il-1β and TnF-α in vitro and in vivo. additionally, overexpression of HMGB1 and/or Tlr4 reversed the anti-inflammatory effects of mir-199a-3p mimics in vitro and in vivo. These results indicate that miR-199a-3p acts as a negative inflammatory regulator in PTB by targeting HMGB1 to regulate the Tlr4/nF-κB pathway.

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“…Prominent examples include NKFBIA , which binds to the nuclear localization signal of the inflammatory response element NF-kappa-B/REL complex, preventing transcription and inflammatory response [53]; and NFIL3 (nuclear factor, interleukin 3 activated), a transcription regulator, mostly inhibiting many genes [54], but also known to activate interleukin-3 [55], mediating pro-B lymphocyte survival [56]. Incidentally, NFKBIA appears to be upregulated in placenta with history of chorioamnionitis, as well as those complicated by preterm premature rupture of membrane (PPROM) cases [57]. Upregulation of NFKBIA is suggested to be a form of anti-inflammatory response to inflammatory insults [57].…”

Section: Discussionmentioning

confidence: 99%

Analysis of two birth tissues provides new insights into the epigenetic landscape of neonates born preterm

Lin

Lim

et al. 2019

Clin Epigenet

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BackgroundPreterm birth (PTB), defined as child birth before completion of 37 weeks of gestation, is a major challenge in perinatal health care and can bear long-term medical and financial burden. Over a million children die each year due to PTB complications, and those who survive can face developmental delays. Unfortunately, our understanding of the molecular pathways associated with PTB remains limited. There is a growing body of evidence suggesting the role of DNA methylation (DNAm) in mediating the effects of PTB on future health outcomes. Thus, epigenome-wide association studies (EWAS), where DNAm sites are examined for associations with PTB, can help shed light on the biological mechanisms linking the two.ResultsIn an Asian cohort of 1019 infants (68 preterm, 951 full term), we examined and compared the associations between PTB and genome-wide DNAm profiles using both cord tissue (n = 1019) and cord blood (n = 332) samples on Infinium HumanMethylation450 arrays. PTB was significantly associated (P < 5.8e−7) with DNAm at 296 CpGs (209 genes) in the cord blood. Over 95% of these CpGs were replicated in other PTB/gestational age EWAS conducted in (cord) blood. This replication was apparent even across populations of different ethnic origin (Asians, Caucasians, and African Americans). More than a third of these 296 CpGs were replicated in at least 4 independent studies, thereby identifying a robust set of PTB-linked epigenetic signatures in cord blood. Interrogation of cord tissue in addition to cord blood provided novel insights into the epigenetic status of the neonates born preterm. Overall, 994 CpGs (608 genes, P < 3.7e−7) associated with PTB in cord tissue, of which only 10 of these CpGs were identified in the analysis using cord blood. Genes from cord tissue showed enrichment of molecular pathways related to fetal growth and development, while those from cord blood showed enrichment of immune response pathways. A substantial number of PTB-associated CpGs from both the birth tissues were also associated with gestational age.ConclusionsOur findings provide insights into the epigenetic landscape of neonates born preterm, and that its status is captured more comprehensively by interrogation of more than one neonatal tissue in tandem. Both these neonatal tissues are clinically relevant in their unique ways and require careful consideration in identification of biomarkers related to PTB and gestational age.Trial registrationThis birth cohort is a prospective observational study designed to study the developmental origins of health and disease, and was retrospectively registered on 1 July 2010 under the identifier NCT01174875.Electronic supplementary materialThe online version of this article (10.1186/s13148-018-0599-4) contains supplementary material, which is available to authorized users.

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Placental TLR/NLR expression signatures are altered with gestational age and inflammation

Cited by 12 publications

References 32 publications

The expression of Toll-like receptor 5 in preterm histologic chorioamnionitis

The expression of Toll-like receptor 5 in preterm histologic chorioamnionitis

miR‑199a‑3p suppresses cervical epithelial cell inflammation by inhibiting the HMGB1/TLR4/NF‑κB pathway in preterm birth

Analysis of two birth tissues provides new insights into the epigenetic landscape of neonates born preterm

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