scholarly journals DREAM Is Involved in the Genesis of Inflammation-Induced Prolabour Mediators in Human Myometrial and Amnion Cells

2018 ◽  
Vol 2018 ◽  
pp. 1-12 ◽  
Author(s):  
Priyanka Goradia ◽  
Ratana Lim ◽  
Martha Lappas
Keyword(s):  
Preterm Birth ◽  
Mrna Expression ◽  
Proinflammatory Cytokine ◽  
Transcriptional Activity ◽  
Regulatory Element ◽  
Poly I:C ◽  
Fetal Membranes ◽  
Perinatal Morbidity ◽  
Viral Dsrna ◽  
Spontaneous Labour

Preterm birth is the primary cause of perinatal morbidity and mortality worldwide. Inflammation induces a cascade of events leading to preterm birth by activating nuclear factor-κB (NF-κB). In nongestational tissues, downstream regulatory element antagonist modulator (DREAM) regulates NF-κB activity. Our aims were to analyse DREAM expression in myometrium and fetal membranes obtained at term and preterm and to determine the effect of DREAM inhibition on prolabour mediators in primary myometrial and amnion cells. DREAM mRNA expression was significantly higher in fetal membranes obtained after spontaneous labour compared to nonlabour and in amnion from women with histological preterm chorioamnionitis when compared to amnion from women without chorioamnionitis. In primary myometrial and amnion cells, the effect of DREAM silencing by siRNA was a significant decrease in the expression of proinflammatory cytokine IL-6, the chemokines IL-8 and MCP-1, the adhesion molecule ICAM-1, MMP-9 mRNA expression and activity, and NF-κB transcriptional activity when stimulated with the proinflammatory cytokine IL-1β, the bacterial products fsl-1 or flagellin, or the viral dsRNA analogue poly(I:C). These data suggest that, in states of heightened inflammation, DREAM mRNA expression is increased and that, in myometrial and amnion cells, DREAM regulates proinflammatory and prolabour mediators which may be mediated via NF-κB.

Optineurin suppression activates the mediators involved in the terminal effector pathways of human labour and delivery

2017 ◽  
Vol 29 (6) ◽  
pp. 1074
Author(s):  
Ratana Lim ◽  
Gillian Barker ◽  
Martha Lappas
Keyword(s):  
Preterm Birth ◽  
Mrna Expression ◽  
Prostaglandin F2α ◽  
Binding Activity ◽  
Negative Regulator ◽  
Fetal Membranes ◽  
Spontaneous Preterm Birth ◽  
Monocyte Chemoattractant Protein 1 ◽  
Myometrial Cells ◽  
Dna Binding Activity

Spontaneous preterm birth remains the major cause of neonatal death and morbidity. Studies in non-gestational tissues report that optineurin (OPTN) is critical in the termination of NFKB1 activity and control of inflammation, central features of spontaneous preterm birth. The aims of the present study were to determine: (1) OPTN expression in fetal membranes and the myometrium during labour; (2) the effects of IL1B on OPTN expression in primary myometrial cells; and (3) the effects of OPTN short interference (si) RNA on IL1B-stimulated proinflammatory and prolabour mediators. OPTN mRNA and protein expression was significantly decreased with spontaneous term labour in fetal membranes and the myometrium. Although there was no effect of spontaneous preterm labour on OPTN expression in fetal membranes, there was decreased OPTN expression in membranes with chorioamnionitis and myometrial cells treated with 1ng mL–1 IL1B for 1 or 6 h. In cells transfected with OPTN siRNA, significant increases were seen in IL1B-stimulated IL6, tumour necrosis factor, CXCL8 and monocyte chemoattractant protein-1 mRNA expression and release, cyclo-oxygenase-2 and prostanoid PTGFR receptor mRNA expression and the release of prostaglandin F2α. There was no change in IL1B-stimulated NFKBIA expression; however, there was increased NFKB1 p65 DNA-binding activity. The results of the present study suggest that OPTN is a negative regulator of inflammation-induced prolabour mediators.

scholarly journals PARK7 regulates inflammation-induced pro-labour mediators in myometrial and amnion cells

Reproduction ◽  
2018 ◽  
Vol 155 (2) ◽  
pp. 207-218 ◽  
Author(s):  
Ratana Lim ◽  
Gillian Barker ◽  
Martha Lappas
Keyword(s):  
Preterm Birth ◽  
Poly I:C ◽  
Fetal Membranes ◽  
Uterine Contractility ◽  
Spontaneous Preterm Birth ◽  
Induced Expression ◽  
Neonatal Deaths ◽  
Myometrial Cells ◽  
Membrane Rupture ◽  
Term Labour

Preterm birth is a prevalent cause of neonatal deaths worldwide. Inflammation has been implicated in spontaneous preterm birth involved in the processes of uterine contractility and membrane rupture. Parkinson protein 7 (PARK7) has been found to play an inflammatory role in non-gestational tissues. The aims of this study were to determine the expression of PARK7 in myometrium and fetal membranes with respect to term labour onset and to elucidate the effect of PARK7 silencing in primary myometrium and amnion cells on pro-inflammatory and pro-labour mediators. PARK7 mRNA expression was higher in term myometrium and fetal membranes from women in labour compared to non-labouring samples and in amnion from preterm deliveries with chorioamnionitis. In human primary myometrial cells transfected with PARK7 siRNA (siPARK7), there was a significant decrease in IL1B, TNF, fsl-1 and poly(I:C)-induced expression of pro-inflammatory cytokine IL6, chemokines (CXCL8, CCL2), adhesion molecule ICAM1, prostaglandin PGF2α and its receptor PTGFR. Similarly, amnion cells transfected with siPARK7 displayed a decrease in IL1B-induced expression of IL6, CXCL8 and ICAM1. In myometrial cells transfected with siPARK7, there was a significant reduction of NF-κB RELA transcriptional activity when stimulated with fsl-1, flagellin and poly(I:C), but not with IL1B or TNF. Collectively, our novel data describe a role for PARK7 in regulating inflammation-induced pro-inflammatory and pro-labour mediators in human myometrial and amnion cells.

scholarly journals KLF5 regulates infection- and inflammation-induced pro-labour mediators in human myometrium

Reproduction ◽  
2015 ◽  
Vol 149 (5) ◽  
pp. 413-424 ◽  
Author(s):  
Martha Lappas
Keyword(s):  
Mrna Expression ◽  
Interleukin 1 ◽  
Poly I:C ◽  
Human Myometrium ◽  
Viral Dsrna ◽  
Myometrial Cells ◽  
Human Labour ◽  
Foetal Membranes ◽  
Term Labour ◽  
Klf5 Expression

The transcription factor Kruppel-like factor 5 (KLF5) has been shown to associate with nuclear factor kappa B (NFκB) to regulate genes involved in inflammation. However, there are no studies on the expression and regulation of KLF5 in the processes of human labour and delivery. Thus, the aims of this study were to determine the effect of i) human labour on KLF5 expression in both foetal membranes and myometrium; ii) the pro-inflammatory cytokine interleukin 1 beta (IL1β), bacterial product flagellin and the viral dsRNA analogue poly(I:C) on KLF5 expression and iii) KLF5 knockdown by siRNA in human myometrial primary cells on pro-inflammatory and pro-labour mediators. In foetal membranes, there was no effect of term or preterm labour on KLF5 expression. In myometrium, the term labour was associated with an increase in nuclear KLF5 protein expression. Moreover, KLF5 expression was also increased in myometrial cells treated with IL1β, flagellin or poly(IC), likely factors contributing to preterm birth. KLF5 silencing in myometrial cells significantly decreased IL1β-induced cytokine expression (IL6 and IL8 mRNA expression and release), COX2 mRNA expression, and subsequent release of prostaglandins PGE2 and PGF2α. KLF5 silencing also significantly reduced flagellin- and poly(I:C)-induced IL6 and IL8 mRNA expression. Lastly, IL1β-, flagellin- and poly(I:C)-stimulated NFκB transcriptional activity was significantly suppressed in KLF5-knockout myometrial cells. In conclusion, this study describes novel data in which KLF5 is increased in labouring myometrium, and KLF5 silencing decreased inflammation- and infection-induced pro-labour mediators.

scholarly journals Preterm Delivery; Who Is at Risk?

2021 ◽  
Vol 10 (11) ◽  
pp. 2279
Author(s):  
Dvora Kluwgant ◽  
Tamar Wainstock ◽  
Eyal Sheiner ◽  
Gali Pariente
Keyword(s):  
Risk Factors ◽  
Preterm Birth ◽  
Prenatal Care ◽  
Recurrent Pregnancy Loss ◽  
Placental Abruption ◽  
Placenta Previa ◽  
Population Based ◽  
Perinatal Morbidity ◽  
Multiple Gestations ◽  
Extremely Preterm

Preterm birth (PTB) is the leading cause of perinatal morbidity and mortality. Adverse effects of preterm birth have a direct correlation with the degree of prematurity, in which infants who are born extremely preterm (24–28 weeks gestation) have the worst outcomes. We sought to determine prominent risk factors for extreme PTB and whether these factors varied between various sub-populations with known risk factors such as previous PTB and multiple gestations. A population-based retrospective cohort study was conducted. Risk factors were examined in cases of extreme PTB in the general population, as well as various sub-groups: singleton and multiple gestations, women with a previous PTB, and women with indicated or induced PTB. A total of 334,415 deliveries were included, of which 1155 (0.35%) were in the extreme PTB group. Placenta previa (OR = 5.8, 95%CI 4.14–8.34, p < 0.001), multiple gestations (OR = 7.7, 95% CI 6.58–9.04, p < 0.001), and placental abruption (OR = 20.6, 95%CI 17.00–24.96, p < 0.001) were the strongest risk factors for extreme PTB. In sub-populations (multiple gestations, women with previous PTB and indicated PTBs), risk factors included placental abruption and previa, lack of prenatal care, and recurrent pregnancy loss. Singleton extreme PTB risk factors included nulliparity, lack of prenatal care, and placental abruption. Placental abruption was the strongest risk factor for extreme preterm birth in all groups, and risk factors did not differ significantly between sub-populations.

Effect of 20-Hydroxyecdysone and S-adenosylmethionine on the ecdysone receptor gene EcR transcriptional activity in housefly Musca domestica L.

Biomics ◽  
2020 ◽  
Vol 12 (4) ◽  
pp. 480-491
Author(s):  
Yu. M. Nikonorov ◽  
T.T. Akhmetkireeva ◽  
G.V. Benkovskaya
Keyword(s):  
Dna Methylation ◽  
Musca Domestica ◽  
Transcriptional Activity ◽  
Regulatory Element ◽  
Receptor Gene ◽  
Tissue Type ◽  
Ecdysone Receptor ◽  
Gender And Age ◽  
The Status ◽  
Terminal Site

Steroid hormone 20-hydroxyecdysone (20E) initiates larval molting start and metamorphosis and regulates reproduction. Its basic receptor is heterodimer including proteins EcR and USP. Ecdysone receptor gene EcR coding protein EcR is a key regulatory element of gene circuits cover considerable part of genes, implicated in growth and development as well as in reproduction of progeny and reactions of organisms to unfavorable factors of environment. The source of methyl groups S-adenosylmethionine (SAM) is in use for biosynthesis of juvenile hormone (JH), methylation of histone proteins and DNA. The main aim of our investigation was evaluation of transcriptional activity of housefly Musca domestica ecdysone receptor gene EcR under adding into ration of 20E and SAM in non-lethal concentrations. Experiments were carried out with larvae and adults of housefly from laboratory strains Shgen and Lgen differ in life span of adults. Change of gene EcR transcripts content in common pool of mRNA in the cells of muscles and gonads, as well as DNA methylation level in 5’-terminal site registered by quantitative real time PCR (RT-PCR). The results of our investigations allow us to suggest existence of mechanism for regulating expression of the EcR gene in M. domestica which is sensitive to exogenic20E and heat stress action as well as to presence of SAM in food. Variations in the mRNA quantitative ratios of EcR gene 5’-and 3’-terminal regions depending on tissue type, gender and age support the hypothesis that this gene can encode several isoforms of the protein EcR. The detected changes in the status of DNA methylation in the 5'-terminal region of the gene and fluctuations in the representation of different mRNA sites after SAM processing suggest the involvement of DNA methylation/demethylation processes in the regulation of EcR gene expression in M. domestica.

scholarly journals Effect of Breed on Transcriptional and Protein Expression of Lipogenic Enzymes in Tail and Subcutaneous Adipose Tissue from Two Grazing Breeds of Lambs

Animals ◽  
2019 ◽  
Vol 9 (2) ◽  
pp. 64
Author(s):  
María Gallardo ◽  
Luis Arias-Darraz ◽  
Juan Cárcamo
Keyword(s):  
Fatty Acid ◽  
Protein Expression ◽  
Mrna Expression ◽  
Fatty Acid Synthase ◽  
Regulatory Element ◽  
Subcutaneous Fat ◽  
Human Consumption ◽  
Meat Industry ◽  
Lipogenic Enzymes ◽  
Expression Levels

This experiment was carried out to determine the effect of breed on mRNA and protein expression levels of lipogenic enzymes acetyl-CoA carboxylase α (ACC), fatty acid synthase (FAS), stearoyl-CoA desaturase 1 (SCD1) plus sterol regulatory element binding transcription factor 1c (SREBP1c) in the subcutaneous fat (SCF) from the back of the animal, and tail fat (TF) of both Chilota and Suffolk Down lambs grazing Calafatal. Eight Chilota and six Suffolk Down 2-month-old male lambs were allocated to graze a “Calafatal”, a typical secondary succession of Chiloé Archipelago, Chile. After 62 d, lambs were slaughtered according to Chile’s meat industry standards. Fatty acid profile, RT-qPCR, and Western blot analyses from SCF and TF samples were performed. Although the mRNA expression levels of ACC, FAS, SCD1 and SREBP1c in SCF did not differ significantly between breeds (p > 0.05), a trend to higher mRNA expression of FAS and SREBP1c in TF from Chilota lambs was observed (p = 0.06). On the other hand, FAS levels in SCF were higher in Chilota than in Suffolk Down lambs (p < 0.02), although Suffolk Down showed higher fat contents and saturated fatty acid (SFA) proportions than Chilota lambs (p < 0.01). The FAS protein expression in TF was similar in both breeds (p > 0.05). Although the fat content was higher in Suffolk Down than in Chilota lambs (p < 0.01), the SFA proportions were similar in both breeds. Finally, it can be concluded that although mRNA expression of enzymes was similar in both breeds, there were differences in some protein levels in the SCF, partially related with the fatty acid profiles, thus affecting the selection of lamb breed either for human consumption or experimental purposes.

scholarly journals FoxO3 regulates hepatic triglyceride metabolism via modulation of the expression of sterol regulatory-element binding protein 1c

2019 ◽  
Vol 18 (1) ◽  
Author(s):  
Liu Wang ◽  
Xiaopeng Zhu ◽  
Xiaoyang Sun ◽  
Xinyu Yang ◽  
Xinxia Chang ◽  
...  
Keyword(s):  
High Fat Diet ◽  
Hepg2 Cells ◽  
Transcriptional Activity ◽  
Regulatory Element ◽  
Luciferase Reporter ◽  
Chow Diet ◽  
Hepatic Triglyceride ◽  
High Fat ◽  
Element Binding Protein ◽  
Sterol Regulatory Element

Abstract Background Excessive intrahepatic lipid accumulation is the major characteristic of nonalcoholic fatty liver disease (NAFLD). We sought to identify the mechanisms involved in hepatic triglyceride (TG) homeostasis. Forkhead box class O (FoxO) transcription factors have been shown to play an important role in hepatic metabolism. However, little is known about the effect of FoxO3 on hepatic TG metabolism. Methods Liver biopsy samples from patients with NALFD and liver tissues from high glucose and high sucrose (HFHS) fed mice, ob/ob mice and db/db mice were collected for protein and mRNA analysis. HepG2 cells were transfected with small interfering RNA to mediate FoxO3 knockdown, or adenovirus and plasmid to mediate FoxO3 overexpression. FoxO3-cDNA was delivered by adenovirus to the liver of C57BL/6 J male mice on a chow diet or on a high-fat diet, followed by determination of hepatic lipid metabolism. Sterol regulatory element-binding protein 1c (SREBP1c) luciferase reporter gene plasmid was co-transfected into HepG2 cells with FoxO3 overexpression plasmid. Results FoxO3 expression was increased in the livers of HFHS mice, ob/ob mice, db/db mice and patients with NAFLD. Knockdown of FoxO3 reduced whereas overexpression of FoxO3 increased cellular TG concentrations in HepG2 cells. FoxO3 gain-of-function caused hepatic TG deposition in C57BL/6 J mice on a chow diet and aggravated hepatic steatosis when fed a high-fat diet. Analysis of the transcripts established the increased expression of genes related to TG synthesis, including SREBP1c, SCD1, FAS, ACC1, GPAM and DGAT2 in mouse liver. Mechanistically, overexpression of FoxO3 stimulated the expression of SREBP1c, whereas knockdown of FoxO3 inhibited the expression of SREBP1c. Luciferase reporter assays showed that SREBP1c regulated the transcriptional activity of the SREBP1c promoter. Conclusions FoxO3 promotes the transcriptional activity of the SREBP1c promoter, thus leading to increased TG synthesis and hepatic TG accumulation.

Sign in / Sign up

Export Citation Format

Share Document