scholarly journals Medium-chain TAG improve intestinal integrity by suppressing toll-like receptor 4, nucleotide-binding oligomerisation domain proteins and necroptosis signalling in weanling piglets challenged with lipopolysaccharide

2018 ◽  
Vol 119 (9) ◽  
pp. 1019-1028 ◽  
Author(s):  
Xiao Xu ◽  
Shaokui Chen ◽  
Haibo Wang ◽  
Zhixiao Tu ◽  
Shuhui Wang ◽  
...  
Keyword(s):  
Protein Expression ◽  
Mrna Expression ◽  
Nucleotide Binding ◽  
Intestinal Morphology ◽  
Toll Like Receptor ◽  
Toll Like Receptor 4 ◽  
Medium Chain ◽  
Intestinal Integrity ◽  
Weanling Piglets ◽  
Maize Oil

AbstractThis study was conducted to evaluate whether medium-chain TAG (MCT) could alleviate Escherichia coli lipopolysaccharide (LPS)-induced intestinal injury by regulating intestinal epithelial inflammatory response, as well as necroptosis. A total of twenty-four weanling piglets were randomly allotted to one of four treatments in a 2×2 factorial arrangement including diet type (5 % maize oil v. 4 % MCT+1 % maize oil) and immune stress (saline v. E. coli LPS). The piglets were fed diets containing maize oil or MCT for 21 d. On 21 d, piglets were injected intraperitoneally with saline or LPS. The blood and intestinal samples were collected at 4 h post injection. Supplementation with MCT improved intestinal morphology, digestive and barrier function, indicated by increased jejunal villus height, increased jejunal and ileal disaccharidases (sucrase and maltase) activities, as well as enhanced protein expression of claudin-1. Furthermore, the protein expression of heat-shock protein 70 in jejunum and the concentration of TNF-α in plasma were reduced in the piglets fed diets supplemented with MCT. In addition, MCT down-regulated the mRNA expression of toll-like receptor 4 (TLR4) and nucleotide-binding oligomerisation domain proteins (NOD) signalling-related genes in jejunum and ileum. Finally, MCT inhibited jejunal and ileal enterocyte necroptosis indicated by suppressed mRNA expression of the receptor-interacting protein 3 and mixed-lineage kinase domain-like protein. These results indicate that MCT supplementation may be closely related to inhibition of TLR4, NOD and necroptosis signalling pathways and concomitant improvement of intestinal integrity under an inflammatory condition.

scholarly journals Asparagine attenuates hepatic injury caused by lipopolysaccharide in weaned piglets associated with modulation of Toll-like receptor 4 and nucleotide-binding oligomerisation domain protein signalling and their negative regulators

2015 ◽  
Vol 114 (2) ◽  
pp. 189-201 ◽  
Author(s):  
Huanting Wu ◽  
Yulan Liu ◽  
Dingan Pi ◽  
Weibo Leng ◽  
Huiling Zhu ◽  
...  
Keyword(s):  
Protein Expression ◽  
Mrna Expression ◽  
Nucleotide Binding ◽  
Toll Like Receptor ◽  
Negative Regulators ◽  
Toll Like Receptor 4 ◽  
Signalling Molecules ◽  
Lps Challenge ◽  
Tnf Α ◽  
Domain Protein

Pro-inflammatory cytokines play a key role in many models of hepatic damage. In addition, asparagine (Asn) plays an important role in immune function. We aimed to investigate whether Asn could attenuate lipopolysaccharide (LPS)-induced liver damage. Forty-eight castrated barrows were allotted to four groups including: (1) non-challenged control; (2) LPS-challenged control; (3) LPS+0·5 % Asn; and (4) LPS+1·0 % Asn. After 19 d feeding with control, 0·5 or 1·0 % Asn diets, pigs were injected with LPS or saline. Blood and liver samples were obtained at 4 h (early stage) and 24 h (late stage) post-injection. Asn alleviated liver injury, indicated by reduced serum aspartate aminotransferase and alkaline phosphatase activities linearly and quadratically; it increased claudin-1 protein expression linearly and quadratically at 24 h, and less severe liver morphological impairment at 4 or 24 h. In addition, Asn decreased mRNA expression of TNF-α and heat shock protein 70 (HSP70) linearly and quadratically at 4 h; it increased TNF-α mRNA expression, and HSP70 protein expression linearly and quadratically at 24 h. Moreover, Asn increased inducible NO synthase activity linearly and quadratically. Finally, Asn down-regulated the mRNA expression of Toll-like receptor 4 (TLR4) signalling molecules (TLR4, IL-1 receptor-associated kinase 1 (IRAK1), TNF-α receptor-associated factor 6), nucleotide-binding oligomerisation domain protein (NOD) signalling molecules (NOD1, NOD2 and their adaptor molecule receptor-interacting serine/threonine-protein kinase 2 (RIPK2)), and NF-κB p65 linearly or quadratically at 4 h. Oppositely, Asn up-regulated mRNA expressions of TLR4 and NOD signalling molecules (TLR4, myeloid differentiation factor 88, IRAK1, NOD2 and RIPK2), and their negative regulators (radioprotective 105, single Ig IL-1R-related molecule, Erbb2 interacting protein and centaurin β1) linearly or quadratically at 24 h. These results indicate that, in early and late stages of LPS challenge, Asn improves liver integrity and exerts different regulatory effects on mRNA expression of TLR4 and NOD signalling molecules.

Effects of dietary lysozyme levels on growth performance, intestinal morphology, non-specific immunity and mRNA expression in weanling piglets

2015 ◽  
Vol 87 (3) ◽  
pp. 411-418 ◽  
Author(s):  
Yanrong Long ◽  
Sen Lin ◽  
Jiatao Zhu ◽  
Xiaoxue Pang ◽  
Zhengfeng Fang ◽  
...  
Keyword(s):  
Growth Performance ◽  
Mrna Expression ◽  
Intestinal Morphology ◽  
Specific Immunity ◽  
Weanling Piglets

Cyclooxygenase 2, toll-like receptor 4 and interleukin 1β mRNA expression in atherosclerotic plaques of type 2 diabetic patients

2014 ◽  
Vol 63 (10) ◽  
pp. 851-858 ◽  
Author(s):  
Alessandro Baldan ◽  
Silvia Ferronato ◽  
Silvia Olivato ◽  
Giovanni Malerba ◽  
Alberto Scuro ◽  
...  
Keyword(s):  
Mrna Expression ◽  
Cyclooxygenase 2 ◽  
Interleukin 1Β ◽  
Diabetic Patients ◽  
Atherosclerotic Plaques ◽  
Toll Like Receptor ◽  
Type 2 Diabetic Patients ◽  
Toll Like Receptor 4 ◽  
Type 2 Diabetic

scholarly journals Lycium barbarum Polysaccharides Promote Maturity of Murine Dendritic Cells through Toll-Like Receptor 4-Erk1/2-Blimp1 Signaling Pathway

2020 ◽  
Vol 2020 ◽  
pp. 1-15
Author(s):  
Xiangguo Duan ◽  
Yaru Lan ◽  
Xiaoyu Zhang ◽  
Shaozhang Hou ◽  
Jian Chen ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Protein Expression ◽  
Molecular Mechanisms ◽  
Signal Molecules ◽  
Toll Like Receptor ◽  
Lycium Barbarum ◽  
Toll Like Receptor 4 ◽  
P38 Inhibitor ◽  
Mrna And Protein Expression ◽  
Lycium Barbarum Polysaccharides

In previous studies, Lycium barbarum polysaccharides (LBP), a traditional Chinese medicine, can promote immature dendritic cells (DCs) to mature. However, the molecular mechanisms by which LBP works are not yet elucidated. Here, we found that LBP can induce DCs maturation, which is mainly characterized by the upregulation of MHCII and costimulatory molecules (CD80, CD86), and increase the production of IL-6 and IL-4. Furthermore, we found that LBP could increase the mRNA and protein expression of TLR4, p38, Erk1/2, JNK, and Blimp1 signal molecules. More interestingly, after blocking by Toll-like receptor 4 inhibitor, Resatorvid (TAK 242), the mRNA and protein expression of TLR4, Erk1/2, and Blimp1 was significantly decreased while the expression of p38 and JNK has not changed. Then, we found that after blocking by p38 inhibitor (SB203580), Erk inhibitor (PD98059), and JNK inhibitor (SP603580) separately, Blimp1 protein expression was significantly reduced; after downregulating Blimp1 by Blimp1-siRNA, the production of IL-6 was reduced. In conclusion, our results indicate that LBP can induce maturation of DCs through the TLR4-Erk1/2-Blimp1 signal pathway instead of the JNK/p38-Blimp1 pathway. Our findings may provide a novel evidence for understanding the molecular mechanisms of LBP on activating murine DCs.

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.

scholarly journals Effect of Carotenoids, Oligosaccharides and Anthocyanins on Growth Performance, Immunological Parameters and Intestinal Morphology in Broiler Chickens Challenged with Escherichia coli Lipopolysaccharide

Animals ◽  
2020 ◽  
Vol 10 (2) ◽  
pp. 347 ◽  
Author(s):  
Brigitta Csernus ◽  
Sándor Biró ◽  
László Babinszky ◽  
István Komlósi ◽  
András Jávor ◽  
...  
Keyword(s):  
Gene Expression ◽  
Escherichia Coli ◽  
Mrna Expression ◽  
Intestinal Morphology ◽  
Interferon Α ◽  
Toll Like Receptor ◽  
Lps Challenge ◽  
Toll Like Receptor 5 ◽  
Relative Mrna Expression ◽  
Escherichia Coli Lipopolysaccharide

This study was conducted to investigate the effect of carotenoid, oligosaccharide and anthocyanin supplementation in broiler diets under Escherichia coli lipopolysaccharide (LPS) challenge. Ross 308 chickens were fed 5 diets: basal diet (control diet), diet supplemented with β-glucan in 0.05% (positive control) and diets with 0.5% carotenoid-, oligosaccharide- or anthocyanin contents. On the 26th days of age, chickens were challenged intraperitoneally 2 mg LPS per kg of body weight. 12 h after injection, birds were euthanized, then spleen and ileum samples were collected. LPS induced increased relative mRNA expression of splenic (p = 0.0445) and ileal (p = 0.0435) interleukin-1β (IL-1β), which was lower in the spleen in carotenoid (p = 0.0114), oligosaccharide (p = 0.0497) and anthocyanin (p = 0.0303)-treated chickens compared to LPS-injected control birds. Dietary supplementation of carotenoids also decreased relative gene expression of splenic interleukin-6 (IL-6) (p = 0.0325). In the ileum, β-glucan supplementation showed lower relative mRNA expression of toll-like receptor 5 (TLR-5) (p = 0.0387) compared to anthocyanin treatment. Gene expression of both splenic and ileal interferon-α (IFN-α), interferon-γ (IFN-γ), toll-like receptor 4 (TLR-4) and toll-like receptor 5 (TLR-5) were not influenced by dietary supplements. In conclusion, carotenoids, oligosaccharides and anthocyanins could partially mitigate the immune stress caused by LPS challenge. All of the compounds impacted longer villus height (p < 0.0001), villus height:crypt depth ratios were higher after β-glucan (p < 0.0001) and anthocyanin (p = 0.0063) supplementations and thickened mucosa was observed in β-glucan (p < 0.0001), oligosaccharide (p < 0.0001) and anthocyanin (p = 0.048) treatments. All of these findings could represent a more effective absorption of nutrients.

Atorvastatin suppresses LPS-induced rapid upregulation of Toll-like receptor 4 and its signaling pathway in endothelial cells

2011 ◽  
Vol 300 (5) ◽  
pp. H1743-H1752 ◽  
Author(s):  
Ying Wang ◽  
Ming Xiang Zhang ◽  
Xiao Meng ◽  
Fu Qiang Liu ◽  
Guang Sheng Yu ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Mrna Expression ◽  
Signaling Pathways ◽  
P38 Mapk ◽  
Umbilical Vein ◽  
Enzyme Linked Immunosorbent Assay ◽  
Toll Like Receptor ◽  
Toll Like Receptor 4 ◽  
Mapk Phosphorylation ◽  
Tlr4 Mrna

In the present study, we tested our hypothesis that atorvastatin exerts its anti-inflammation effect via suppressing LPS-induced rapid upregulation of Toll-like receptor 4 (TLR4) mRNA and its downstream p38, ERK, and NF-κB signaling pathways in human umbilical-vein endothelial cells (HUVECs) and human aortic endothelial cells (HAECs). TLR4 mRNA expression and its downstream kinase activities induced by LPS alone or atorvastatin + LPS in endothelial cells were quantified using quantitative real-time PCR and enzyme-linked immunosorbent assay. Preincubation of LPS-stimulated endothelial cells with TLR4 siRNA was conducted to identify the target of the anti-inflammatory effects of atorvastatin. Atorvastatin incubation resulted in the reduction of LPS-induced TLR4 mRNA expression, ERK1/2 and P38 MAPK phosphorylation, and NF-κB binding activity. Pretreatment with MEK/ERK1/2 inhibitor PD98059 attenuated atorvastatin + LPS-induced NF-κB activity but had no effect on P38 MAPK phosphorylation. In contrast, pretreatment with P38 MAPK inhibitor SB203580 resulted in upregulation of atorvastatin + LPS-induced ERK1/2 phosphorylation but had no significant effects on NF-κB activity. On the other hand, blocking NF-κB with SN50 produced no effects on atorvastatin + LPS-induced ERK1/2 and P38 MAPK phosphorylation. Moreover, TLR4 gene silencing produced the same effects as the atorvastatin treatment. In conclusion, atorvastatin downregulated TLR4 mRNA expression by two distinct signaling pathways. First, atorvastatin stabilized Iκ-Bα, which directly inhibited NF-κB activation. Second, atorvastatin inactivated ERK phosphorylation, which indirectly inhibited NF-κB activation. Suppression of p38 MAPK by atorvastatin upregulates ERK but exerts no effect on NF-κB.

Developmental changes in hypothalamic toll‐like‐receptor 4 mRNA expression and the effects of lipopolysaccharide on such changes in female rats

2014 ◽  
Vol 40 (1) ◽  
pp. 12-14 ◽  
Author(s):  
Takeshi Iwasa ◽  
Toshiya Matsuzaki ◽  
Altankhuu Tungalagsuvd ◽  
Munkhsaikhan Munkhzaya ◽  
Takako Kawami ◽  
...  
Keyword(s):  
Mrna Expression ◽  
Developmental Changes ◽  
Female Rats ◽  
Toll Like Receptor ◽  
Toll Like Receptor 4

Vitamin D inhibits lipopolysaccharide-induced inflammatory response potentially through the Toll-like receptor 4 signalling pathway in the intestine and enterocytes of juvenile Jian carp (Cyprinus carpio var. Jian)

2015 ◽  
Vol 114 (10) ◽  
pp. 1560-1568 ◽  
Author(s):  
Jun Jiang ◽  
Dan Shi ◽  
Xiao-Qiu Zhou ◽  
Long Yin ◽  
Lin Feng ◽  
...  
Keyword(s):  
Vitamin D ◽  
Inflammatory Response ◽  
Mrna Expression ◽  
Toll Like Receptor ◽  
Toll Like Receptor 4 ◽  
Jian Carp ◽  
Pre Treatment ◽  
Inflammatory Effect

AbstractThe present study was conducted to investigate the anti-inflammatory effect of vitamin D both in juvenile Jian carp (Cyprinus carpio var. Jian) in vivo and in enterocytes in vitro. In primary enterocytes, exposure to 10 mg lipopolysaccharide (LPS)/l increased lactate dehydrogenase activity in the culture medium (P<0·05) and resulted in a significant loss of cell viability (P<0·05). LPS exposure increased (P<0·05) the mRNA expression of pro-inflammatory cytokines (TNF-α, IL-1β, IL-6 and IL-8), which was decreased by pre-treatment with 1,25-dihydroxyvitamin D (1,25D3) in a dose-dependent manner (P<0·05). Further results showed that pre-treatment with 1,25D3 down-regulated Toll-like receptor 4 (TLR4), myeloid differentiation primary response gene 88 (Myd88) and NF-κB p65 mRNA expression (P<0·05), suggesting potential mechanisms against LPS-induced inflammatory response. In vivo, intraperitoneal injection of LPS significantly increased TNF-α, IL-1β, IL-6 and IL-8 mRNA expression in the intestine of carp (P<0·05). Pre-treatment of fish with vitamin D3 protected the fish intestine from the LPS-induced increase of TNF-α, IL-1β, IL-6 and IL-8 mainly by downregulating TLR4, Myd88 and NF-κB p65 mRNA expression (P<0·05). These observations suggest that vitamin D could inhibit LPS-induced inflammatory response in juvenile Jian carp in vivo and in enterocytes in vitro. The anti-inflammatory effect of vitamin D is mediated at least in part by TLR4-Myd88 signalling pathways in the intestine and enterocytes of juvenile Jian carp.

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