Functional Screening of TLRs in Human Amniotic Epithelial Cells

Gillaux, Claire; Méhats, Céline; Vaiman, Daniel; Cabrol, D.; Breuiller-Fouché, Michelle

doi:10.4049/jimmunol.1100217

Cited by 71 publications

(91 citation statements)

References 59 publications

(61 reference statements)

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“…Thus, the differential expression of infection- or inflammation-related genes in our study could be attributed to a combination of infection and labor. For example, inflammatory-related genes and their respective proteins such as NFKB1 [48], CCR1 [49], SOCS3, JAK3 [50], JUNB [51], RHOG [52], TIMP1 [53], IL1beta [54]–[57], ITGAM [58], CD44 [59], [60], TLR5 [61]–[63] and CXCR1 [64], [65] from our Reactome analysis are known to be up-regulated in reproductive tissues and other biologic fluids during term labor or PTL with or without infection. CD63 was increased in our study but fetal blood CD63 was not associated with sPTB [66].…”

Section: Discussionmentioning

confidence: 99%

Whole Blood Gene Expression Profile Associated with Spontaneous Preterm Birth in Women with Threatened Preterm Labor

et al. 2014

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Threatened preterm labor (TPTL) is defined as persistent premature uterine contractions between 20 and 37 weeks of gestation and is the most common condition that requires hospitalization during pregnancy. Most of these TPTL women continue their pregnancies to term while only an estimated 5% will deliver a premature baby within ten days. The aim of this work was to study differential whole blood gene expression associated with spontaneous preterm birth (sPTB) within 48 hours of hospital admission. Peripheral blood was collected at point of hospital admission from 154 women with TPTL before any medical treatment. Microarrays were utilized to investigate differential whole blood gene expression between TPTL women who did (n = 48) or did not have a sPTB (n = 106) within 48 hours of admission. Total leukocyte and neutrophil counts were significantly higher (35% and 41% respectively) in women who had sPTB than women who did not deliver within 48 hours (p<0.001). Fetal fibronectin (fFN) test was performed on 62 women. There was no difference in the urine, vaginal and placental microbiology and histopathology reports between the two groups of women. There were 469 significant differentially expressed genes (FDR<0.05); 28 differentially expressed genes were chosen for microarray validation using qRT-PCR and 20 out of 28 genes were successfully validated (p<0.05). An optimal random forest classifier model to predict sPTB was achieved using the top nine differentially expressed genes coupled with peripheral clinical blood data (sensitivity 70.8%, specificity 75.5%). These differentially expressed genes may further elucidate the underlying mechanisms of sPTB and pave the way for future systems biology studies to predict sPTB.

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Section: Discussionmentioning

confidence: 99%

Whole Blood Gene Expression Profile Associated with Spontaneous Preterm Birth in Women with Threatened Preterm Labor

et al. 2014

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“…20 In addition, TLR4/NF-κB signaling pathway is also considered to be a major signal transduction pathway involved in apoptosis. 21,[26][27] It has been found that LPS caused IEC apoptosis through a TLR4-dependent mechanism.…”

Section: Discussionmentioning

confidence: 99%

“…[21][22]27 At present, TLR4/ NF-κB pathway has been believed as a targets for IBD control. 28 The results of this study demonstrated that CHOS treatment significantly downregulated the enhanced expression of TLR4 and NF-κB induced by LPS, suggesting the possible involvement of this signal pathway in the protective role of CHOS against IBD.…”

Section: Discussionmentioning

confidence: 99%

Chitooligosaccharides Attenuate Lipopolysaccharideinduced Inflammation and Apoptosis of Intestinal Epithelial Cells: Possible Involvement of TLR4/NF-κB Pathway.

Yang¹,

Tong²,

Luo³

et al. 2016

IJPER

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Marine-derived chitooligosaccharides (CHOS) are a new class of anti-inflammatory natural products characterized by its nontoxity, low-cost and small-molecule. But whether CHOS exert a protective action against inflammatory bowel diseases (IBDs) is not yet fully understood. This paper studied the effect of CHOS on the inflammation and apoptosis of intestinal epithelial cells (IECs) using lipopolysaccharides (LPS)-stimulated Caco-2 cells as an in vitro model of IBD. Caco-2 cells were pre-incubated with various concentrations of CHOS (0.25, 0.5 and 1.0 mg/ml) for 2 h prior to being co-stimulated or not with LPS at a concentration of 1µg/mL for 48h. Cell apoptosis was measured with Annexin V-FITC and propidium iodide (PI) assay by flow cytometry. The levels of proinflammatory mediators including tumor necrosis factor (TNF)-α, interleukin-8 and prostaglandin (PG) E2 were analyzed using Enzyme-linked Immunosorbent Assay. And the cell expression of toll-like receptor 4 (TLR4), nuclear factor kappa B (NF-κB), caspase-3, bcl-2, and cyclooxygenase (COX)-2 was examined by western blot. We observed that CHOS significantly and concentration-dependently inhibited the LPS-induced inflammatory response and apoptosis of IECs, which was evidenced by the reduction in the release of proinflammatory mediators TNF-α, PGE2, the expression of COX-2, apoptotic (Annexin V + /PI -) cell populations, the pro-apoptotic caspase-3 expression, and the enhancement of the expression level of anti-apoptotic bcl-2. And CHOS treatment significantly reduced the protein expressions of TLR4 and NF-κB in LPS-stimulated Caco-2 cells. Thus, the present study suggests the potential medical use of CHOS in the control of IBDs, which may be due to the downregulation of TLR4/NF-κB pathway.

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“…In vitro studies have demonstrated that human primary amnion epithelial cells express functional TLR-2, TLR-4, TLR-5, and TLR-6 and that stimulation with TLR-5 and TLR-2/6 agonists leads to activation of nuclear factor kappa B signaling and the production of proinflammatory cytokines, MMP-9, and PGS2 (57). These findings are consistent with human studies and animal models of chorioamnionitis/intrauterine infection, which demonstrate an increase in IL-1␤ and IL-6 (58, 59), IL-8 (52), tumor necrosis factor alpha (TNF-␣) (60), monocyte chemotactic proteins (61), and granulocyte colony-stimulating factor (G-CSF) (62) in preterm fetal membranes, amniotic fluid, and/or cord blood.…”

Section: Figmentioning

confidence: 99%

The Human Ureaplasma Species as Causative Agents of Chorioamnionitis

et al. 2017

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SUMMARY The human Ureaplasma species are the most frequently isolated microorganisms from the amniotic fluid and placentae of women who deliver preterm and are also associated with spontaneous abortions or miscarriages, neonatal respiratory diseases, and chorioamnionitis. Despite the fact that these microorganisms have been habitually found within placentae of pregnancies with chorioamnionitis, the role of Ureaplasma species as a causative agent has not been satisfactorily explained. There is also controversy surrounding their role in disease, particularly as not all women infected with Ureaplasma spp. develop chorioamnionitis. In this review, we provide evidence that Ureaplasma spp. are associated with diseases of pregnancy and discuss recent findings which demonstrate that Ureaplasma spp. are associated with chorioamnionitis, regardless of gestational age at the time of delivery. Here, we also discuss the proposed major virulence factors of Ureaplasma spp., with a focus on the multiple-banded antigen (MBA), which may facilitate modulation/alteration of the host immune response and potentially explain why only subpopulations of infected women experience adverse pregnancy outcomes. The information presented within this review confirms that Ureaplasma spp. are not simply “innocent bystanders” in disease and highlights that these microorganisms are an often underestimated pathogen of pregnancy.

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Functional Screening of TLRs in Human Amniotic Epithelial Cells

Cited by 71 publications

References 59 publications

Whole Blood Gene Expression Profile Associated with Spontaneous Preterm Birth in Women with Threatened Preterm Labor

Whole Blood Gene Expression Profile Associated with Spontaneous Preterm Birth in Women with Threatened Preterm Labor

Chitooligosaccharides Attenuate Lipopolysaccharideinduced Inflammation and Apoptosis of Intestinal Epithelial Cells: Possible Involvement of TLR4/NF-κB Pathway.

The Human Ureaplasma Species as Causative Agents of Chorioamnionitis

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