scholarly journals Intra-uterine Growth Restriction Downregulates the Hepatic Toll Like Receptor-4 Expression and Function

2005 ◽  
Vol 12 (1) ◽  
pp. 59-66 ◽  
Author(s):  
Ozlem Equils ◽  
Sapna Singh ◽  
Semra Karaburun ◽  
Daning Lu ◽  
Manikkavasagar Thamotharan ◽  
...  
Keyword(s):  
Mrna Expression ◽  
Growth Restriction ◽  
Milk Intake ◽  
Mrna Levels ◽  
Toll Like Receptor ◽  
Tlr4 Expression ◽  
Tlr4 Mrna ◽  
Increased Risk ◽  
Tnf Α ◽  
And Function

Maternal starvation is a significant cause of intrauterine growth restriction (IUGR) in the world and increases the risk of infection in the neonate. We examined the effect of maternal starvation on Toll like receptor (TLR)4 expression in hepatic, splenic and intestinal tissues obtained from the adult IUGR offspring of prenatal calorie restricted rats. The hepatic TLR4 protein concentration was undetectable in the IUGR rats that had restricted milk intake during the suckling period (SM/SP;n= 4,p< 0.05) as compared to the normal growth controls (CM/CP;n=4), and access to ad lib milk intake during the sucking period partially corrected the hepatic TLR4 expression (SM/CP;n= 4). IUGR had no effect on the splenic (n= 4) or intestinal (n= 4) TLR4 mRNA levels. In the liver, IUGR led to a 20% increase in baseline tumor necrosis factor (TNF)-α mRNA expression (p< 0.03) and a 70% increase in interleukin-1β (IL-1β) mRNA expression (p< 0.008) as compared to the control rats (CM/CP;n= 7). LPS-induced hepatic TNF-α release was significantly higher in SM/SP as compared to CM/CP. We propose that IUGR dysregulates TLR4 expression and function in the offspring, which may help explain the increased risk of Gram-negative sepsis and inflammatory diseases in this population.

scholarly journals The Expression of Toll-Like Receptor 4 mRNA in PBMCs Is Upregulated in Smokers and Decreases Upon Smoking Cessation

2021 ◽  
Vol 12 ◽  
Author(s):  
Hsin-Yu Yeh ◽  
Shou-Hung Hung ◽  
Su-Chiu Chen ◽  
Fei-Ran Guo ◽  
Hsien-Liang Huang ◽  
...  
Keyword(s):  
Smoking Cessation ◽  
Cigarette Smoking ◽  
Mrna Expression ◽  
Mononuclear Cells ◽  
Intercellular Adhesion Molecule ◽  
Mrna Levels ◽  
Toll Like Receptor ◽  
Toll Like Receptor 4 ◽  
Tlr4 Mrna ◽  
Tnf Α

BackgroundStudies have shown in vitro that cigarette smoke condensate stimulates monocytes to express toll-like receptor 4 (TLR4), tumor necrosis factor-α (TNF-α), and intercellular adhesion molecule 1 (ICAM-1), and enhances their adhesion to the endothelium. However, the same effects of cigarette smoking have not been explored in vivo. This study is to investigate the effect of cigarette smoking and smoking cessation on their mRNA expression in human peripheral blood mononuclear cells (PBMCs).MethodsA group of 97 smokers and 62 nonsmokers were enrolled. The RNA from PBMCs was assessed with real-time polymerase chain reaction (PCR) to determine the levels of ICAM-1, TNF-α, and TLR4. The same markers in PBMCs of 87 quitters were examined before and at one week, one month, and two months after smoking cessation.ResultsOf the 97 smokers, 85 (87.6%) were males, and 30 (48.4%) of the nonsmokers were males (p &lt; 0.0001). The mean (SD) age of the smokers was 43.24 (10.89) years, which was younger than 43.45 (11.41) years of nonsmokers (p &lt; 0.0001). The incidence of cardiovascular diseases was 13.4% in smokers, which was higher than 1.6% in nonsmokers (p &lt; 0.05). Both ICAM-1 and TNF-α mRNA levels in PBMCs were higher among the smokers (p &lt; 0.0001). In addition, TLR4 mRNA levels in PBMCs were statistically elevated in the smokers (p &lt; 0.0001) comparing with those in the nonsmokers. The mRNA levels of TLR4 and TNF-α in PBMCs decreased in those who had quit smoking for 2 months (p &lt; 0.0001).ConclusionsICAM-1, TNF-α, and TLR4 mRNA expression levels in PBMCs increased in smokers and decreased after being on a smoking cessation program for 2 months. This finding suggested that TLR4 expression may mediate the atherogenic inflammatory process induced by smoking.

Toll-like receptor 4 and CD14 mRNA expression are lower in resistive exercise-trained elderly women

2003 ◽  
Vol 95 (5) ◽  
pp. 1833-1842 ◽  
Author(s):  
Michael G. Flynn ◽  
Brian K. McFarlin ◽  
Melody D. Phillips ◽  
Laura K. Stewart ◽  
Kyle L. Timmerman
Keyword(s):  
Mrna Expression ◽  
Group Effect ◽  
Toll Like Receptor ◽  
Significant Group Effect ◽  
Toll Like Receptor 4 ◽  
Significant Group ◽  
Resistive Exercise ◽  
Tlr4 Mrna ◽  
Tnf Α ◽  
Cd14 Mrna

The purpose of this study was to examine the influence of resistive exercise training and hormone status on mRNA expression of toll-like receptor 4 (TLR4), CD14, IL-1β, IL-6, and TNF-α. Resistive exercise-trained women on “traditional” hormone replacements [hormone replacement therapy (HRT), n = 9], not taking hormones (NHR, n = 6), or taking medications known to influence bone (MIB, n = 7) were compared with untrained subjects not taking supplemental hormones (Con, n = 6). Blood was taken from trained subjects before, immediately after, and 2 h after resistive exercise (same time points for resting Con). TLR4 mRNA expression (RT-PCR) was not different among groups or across time but was significantly ( P = 0.044) lower (1.9-fold) when trained groups were collapsed and compared with Con. There was also a significant group effect ( P < 0.0001) for TLR4 mRNA when expressed per monocyte. CD14 expression was significantly ( P = 0.006) lower (2.3-fold) for training groups collapsed and compared with Con. CD14 mRNA, expressed per monocyte, was significantly lower immediately after resistive exercise for NHR, HRT, and MIB compared with Con. There were few significant effects detected for IL-6, IL-1β, and TNF-α mRNA, but there was a significant group effect ( P < 0.0001) for TNF-α mRNA expressed per monocyte (Con > HRT, NHR, MIB). These findings suggest that there may be a resistive exercise training-induced reduction in TLR4/CD14 expression in older women. Further research is needed to determine whether lower TLR4/CD14 could explain the lower LPS-stimulated inflammatory cytokines observed in these women.

Abstract 978: Novel Endothelial-protective Effect of High Density Lipoprotein: Down-regulation of Toll-like Receptor 4

Circulation ◽  
2007 ◽  
Vol 116 (suppl_16) ◽  
Author(s):  
Frank Spillmann ◽  
Sophie Van Linthout ◽  
Aysun Subasigüller ◽  
Carola Bücker-Gärtner ◽  
Meloni Meloni ◽  
...  
Keyword(s):  
Mrna Expression ◽  
Endotoxic Shock ◽  
Weight Ratio ◽  
Neutrophil Infiltration ◽  
Myeloperoxidase Activity ◽  
Toll Like Receptor ◽  
Tlr4 Expression ◽  
Neutrophil Sequestration ◽  
Tlr4 Mrna ◽  
Apo Ai

Introduction: Endothelium-derived Toll-like receptor (TLR) 4 is known to be the key molecule in lipopolysaccharide (LPS)-induced neutrophil sequestration into lungs. The aim of our study was to investigate whether the endothelial-protective effects of HDL also include regulation of Toll-like receptor (TLR) 4. Therefore, we analyzed the effect of HDL supplementation on TLR4 expression in human aortic endothelial cells (HAEC) and the effect of increased HDL following adenoviral apo AI ( Ad.AI) gene transfer (GT) on lung TLR4 expression in an experimental model of LPS-induced endotoxic shock. Methods: HDL (50 μg/ml) was supplemented to HAEC in the presence/absence of LPS (100 ng/ml). Surface-TLR4 expression on HAEC was analyzed by FACS. C57BL/6 mice were i.v. injected with 5 x 10 10 total particles of Ad.AI or with Ad.Null . Fourteen days hereafter, mice were i.p. injected with LPS (80 mg/kg) or with saline and 20 hours afterwards sacrificed. For survival studies, endotoxic shock was induced in 25 mice per group. Lung myeloperoxidase activity (MPO), as a marker of neutrophil infiltration was analysed. Lung TLR4-mRNA expression was determined by real-time PCR, plasma interferon-gamma (INFγ) levels by ELISA. Results: HDL supplementation significantly reduced TLR4 expression on HAEC. Ad.AI resulted in human apo AI expression levels of 80 ± 10 mg/dl at day 14. By 24 hours after LPS injection, 81% of LPS-treated Ad.Null and saline mice died, in contrast to 50% of Ad.AI LPS-treated mice. This was associated with a 1.6- and 1.7-fold (p<0.05) lower lung/body weight ratio in Ad.AI compared to Ad.Null and saline LPS-injected mice. LPS-induced lung TLR4 mRNA expression was 2.0-fold (p<0.05) reduced after human apo AI-GT compared to LPS controls. Moreover, human apo AI-GT significantly reduced neutrophil infiltration in LPS-treated mice, as indicated by 1.8-fold (p<0.05) and 1.9-fold (p<0.05) reduced MPO activity compared to controls, respectively. Plasma INFγ-levels were 2.8-fold and 2.2-fold (p<0.05) lower versus LPS-treated Ad.Null and saline mice, respectively. Conclusion: The HDL-mediated reduction in lung TLR4 expression contributes for the reduced neutrophil infiltration and subsequently may account for improved mortality rate.

Hepatic IGF1 DNA methylation is influenced by gender but not by intrauterine growth restriction in the young lamb

2015 ◽  
Vol 6 (6) ◽  
pp. 558-572 ◽  
Author(s):  
D. J. Carr ◽  
J. S. Milne ◽  
R. P. Aitken ◽  
C. L. Adam ◽  
J. M. Wallace
Keyword(s):  
Dna Methylation ◽  
Growth Hormone ◽  
Sexual Dimorphism ◽  
Mrna Expression ◽  
Intrauterine Growth Restriction ◽  
Messenger Rna ◽  
Methylation Status ◽  
Growth Restriction ◽  
Intrauterine Growth ◽  
Increased Risk

Intrauterine growth restriction (IUGR) and postnatal catch-up growth confer an increased risk of adult-onset disease. Overnourishment of adolescent ewes generates IUGR in ∼50% of lambs, which subsequently exhibit increased fractional growth rates. We investigated putative epigenetic changes underlying this early postnatal phenotype by quantifying gene-specific methylation at cytosine:guanine (CpG) dinucleotides. Hepatic DNA/RNA was extracted from IUGR [eight male (M)/nine female (F)] and normal birth weight (12 M/9 F) lambs. Polymerase chain reaction was performed using primers targeting CpG islands in 10 genes: insulin, growth hormone, insulin-like growth factor (IGF)1, IGF2, H19, insulin receptor, growth hormone receptor, IGF receptors 1 and 2, and the glucocorticoid receptor. Using pyrosequencing, methylation status was determined by quantifying cytosine:thymine ratios at 57 CpG sites. Messenger RNA (mRNA) expression of IGF system genes and plasma IGF1/insulin were determined. DNA methylation was independent of IUGR status but sexual dimorphism in IGF1 methylation was evident (M<F, P=0.008). IGF1 mRNA:18S and plasma IGF1 were M>F (both P<0.001). IGF1 mRNA expression correlated negatively with IGF1 methylation (r=−0.507, P=0.002) and positively with plasma IGF1 (r=0.884, P<0.001). Carcass and empty body weights were greater in males (P=0.002–0.014) and this gender difference in early body conformation was mirrored by sexual dimorphism in hepatic IGF1 DNA methylation, mRNA expression and plasma IGF1 concentrations.

Changes in Toll-like Receptor (TLR)-2 and TLR4 Expression and Function but Not Polymorphisms Are Associated with Acute Anterior Uveitis

2007 ◽  
Vol 48 (4) ◽  
pp. 1711 ◽  
Author(s):  
John H. Chang ◽  
Taline Hampartzoumian ◽  
Beth Everett ◽  
Andrew Lloyd ◽  
Peter J. McCluskey ◽  
...  
Keyword(s):  
Anterior Uveitis ◽  
Toll Like Receptor ◽  
Tlr4 Expression ◽  
Acute Anterior Uveitis ◽  
And Function

scholarly journals Sini Decoction Improves Adrenal Function and the Short-Term Outcome of Septic Rats through Downregulation of Adrenal Toll-Like Receptor 4 Expression

2018 ◽  
Vol 2018 ◽  
pp. 1-9 ◽  
Author(s):  
Fang Lai ◽  
Gengbiao Zhou ◽  
Shutao Mai ◽  
Xiaolian Qin ◽  
Wenting Liu ◽  
...  
Keyword(s):  
Overall Survival ◽  
Survival Rate ◽  
Mrna Expression ◽  
Adrenal Insufficiency ◽  
Adrenal Glands ◽  
Group Versus ◽  
Mrna Levels ◽  
Toll Like Receptor ◽  
Adrenal Tissue ◽  
The Impact

Background. Sini Decoction (SND) is composed of Aconitum carmichaelii Debeaux, Zingiber officinale Roscoe, and Glycyrrhiza uralensis Fisch, having been used in China for centuries for collapsing phrase of disease. Studies reported that SND could alleviate inflammatory response, ameliorate microcirculatory disturbances, and improve shock reversal and adrenal gland glucocorticoid stress response during sepsis shock, yet the underlying mechanism is still elusive. Toll-like receptor (TLR) 4 is demonstrated to be crucially correlated with the corticosterone secretion and the impaired adrenal glucocorticoid responses in sepsis. Materials and Methods. SND at dose of 10 g/kg (in low-dose SND group, LD-SND) and 20 g/kg (in high-dose SND group, HD-SND) was administered to CLP rats. Four days later, overall survival rates of rats were calculated; rat serum and adrenal glands were collected. Basic serum corticosterone levels were determined, and the increase of corticosterone after 0.8 ug/kg ACTH injection was checked to detect the adrenocortical sensitivity to ACTH. The protein and mRNA expression of TLR4 in adrenal glands were measured to study the impact of SND on TLR4 expression. mRNA levels of IL-10 and TNF-a in adrenal glands and IL-10 and TNF-a levels in serum were also determined to study the cytokines profile. Results. SND improved the cumulative survival rate of CLP rats up to 4 days (P < 0.05 with HD-SND) and adrenocortical sensitivity to 0.8 ug/kg ACTH stimulation (P < 0.05 at 60 mins, 31.02 ± 19.23 ng/ml in LD-SND group and 32.18 ± 14.88 ng/ml in HD-SND group versus 5.03 ± 13.34 ng/ml in CLP group), with a significant decrease of protein (P < 0.05, 29.6% in LD-SND group and 27.8% in HD-SND group), mRNA expression of TLR4 (P < 0.05, 32.9% in LD-SND group and 36.1% in HD-SND group), mRNA expression of IL-10 (P < 0.05, 32.0% in LD-SND group and 29.6% in HD-SND group), TNF-a in adrenal glands (P < 0.05, 26.0% in LD-SND group and 25.3% in HD-SND group), and TNF-a level in serum (P < 0.05, 100.20 ± 19.41 pg/ml in LD-SND group and 92.40 ± 11.66 pg/ml in HD-SND group versus 134.40 ± 27.87 pg/ml in CLP group). Conclusion. SND increased overall survival rate within 4 days and attenuated adrenal insufficiency in septic rats by downregulating TLR4 mRNA and protein expression in adrenal tissue, inhibiting adrenal production of TNF-α and IL-10, and improving adrenal responsiveness. Our results suggest that SND is able to ameliorate adrenal stress responses in a local immune-adrenal crosstalk way involving downregulated expression of TLR4 in adrenal tissue. SND might be a promising treatment for adrenal insufficiency prevention in prolonged sepsis.

Oxymatrine inhibits lipopolysaccharide-induced inflammation by down-regulating Toll-like receptor 4/nuclear factor-kappa B in macrophages

2015 ◽  
Vol 93 (4) ◽  
pp. 253-260 ◽  
Author(s):  
Yu Zhang ◽  
Ruhong Yan ◽  
Yae Hu
Keyword(s):  
Nitric Oxide ◽  
Interleukin 1 ◽  
Chinese Herb ◽  
Mrna Levels ◽  
Nuclear Factor ◽  
Toll Like Receptor ◽  
Toll Like Receptor 4 ◽  
Necrosis Factor Alpha ◽  
Tnf Α ◽  
Anti Inflammatory

Oxymatrine (OMT) is the quinolizidine alkaloid extracted from the Chinese herb Sophora flavescens Ait. that has many pharmacological effects and is used for the treatment of some inflammatory diseases. In this study, RAW264.7 cells and THP-1 differentiated macrophages were pretreated with various concentrations of OMT at 2 h prior to treatment with lipopolysaccharide (LPS) (1.0 μg/mL) for different durations. We detected the anti-inflammatory effect of OMT in LPS-stimulated macrophages and investigated the molecular mechanism. We showed that OMT pretreatment significantly inhibited the LPS-induced secretion of nitric oxide (NO), interleukin-1 beta (IL-1β), and tumor necrosis factor-alpha (TNF-α) in supernatant, attenuated the mRNA levels of inducible nitric oxide synthase (iNOS), IL-1β, TNF-α, and Toll-like receptor 4 (TLR4), increased TLR4 and phosphorylation of inhibitor of kappa B-alpha (p-IBα) in cytosol, and decreased the nuclear level of nuclear factor-κB (NF-κB) p65 in macrophages. In conclusion, OMT exerts anti-inflammatory properties in LPS-stimulated macrophages by down-regulating the TLR4/NF-κB pathway.

scholarly journals Beneficial effects of inhaled nitric oxide with intravenous steroid in an ischemia–reperfusion model involving aortic clamping

2018 ◽  
Vol 31 ◽  
pp. 039463201775148 ◽  
Author(s):  
Waldemar Gozdzik ◽  
Stanisław Zielinski ◽  
Marzena Zielinska ◽  
Kornel Ratajczak ◽  
Piotr Skrzypczak ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Inflammatory Response ◽  
Mrna Expression ◽  
Oxygen Delivery ◽  
Ischemia Reperfusion ◽  
Systemic Inflammatory Response ◽  
Inhaled Nitric Oxide ◽  
Tlr4 Expression ◽  
Sham Surgery ◽  
Tlr4 Mrna

This study evaluated the effects of inhaled nitric oxide (iNO) therapy combined with intravenous (IV) corticosteroids on hemodynamics, selected cytokines, and kidney messenger RNA toll-like receptor 4 (mRNA TLR4) expression in ischemia–reperfusion injury animal model. The primary endpoint was the evaluation of circulatory, respiratory, and renal function over time. We also investigated the profile of selected cytokines and high-mobility group box 1 (HMGB1) protein, as well as renal mRNA TLR4 activation determined by quantitative real-time polymerase chain reaction analysis. Pigs (n = 19) under sevoflurane AnaConDa anesthesia/sedation were randomized and subjected to abdominal laparotomy and alternatively suprarenal aortic cross-clamping (SRACC) for 90 min or sham surgery: Group 1 (n = 8) iNO (80 ppm) + IV corticosteroids (25 mg ×3) started 30 min before SRACC and continued 2 h after SRACC release, followed with decreased iNO (30 ppm) until the end of observation, Group 2 (n = 8) 90 min SRACC, Group 3 (n = 3)—sham surgery. Renal biopsies were sampled 1 hr before SRACC and at 3 and 20 h after SRACC release. Aortic clamping increased TLR4 mRNA expression in ischemic kidneys, but significant changes were recorded only in the control group ( P = 0.016). Treatment with iNO and hydrocortisone reduced TLR4 mRNA expression to pre-ischemic conditions, and the difference observed in mRNA expression was significant between control and treatment group after 3 h ( P = 0.042). Moreover, animals subjected to treatment with iNO and hydrocortisone displayed an attenuated systemic inflammatory response and lowered pulmonary vascular resistance plus increased oxygen delivery. The results indicated that iNO therapy combined with IV corticosteroids improved central and systemic hemodynamics, oxygen delivery, and diminished the systemic inflammatory response and renal mRNA TLR4 expression.

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