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Anti-viral role of toll like receptor 4 in hepatitis B virus infection: An in vitro study 被引量:4
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作者 Dipanwita Das Neelakshi Sarkar +7 位作者 Isha Sengupta Ananya Pal Debraj Saha Manikankana Bandopadhyay Chandrima Das Jimmy Narayan Shivram Prasad Singh Runu Chakravarty 《World Journal of Gastroenterology》 SCIE CAS 2016年第47期10341-10352,共12页
AIM Toll like receptors plays a significant anti-viral role in different infections. The aim of this study was to look into the role of toll like receptor 4(TLR4) in hepatitis B virus(HBV) infection.METHODS Real time ... AIM Toll like receptors plays a significant anti-viral role in different infections. The aim of this study was to look into the role of toll like receptor 4(TLR4) in hepatitis B virus(HBV) infection.METHODS Real time PCR was used to analyze the transcription of TLR4 signaling molecules, cell cycle regulators and HBV DNA viral load after triggering the Hep G2.2.15 cells with TLR4 specific ligand. Nuclear factor(NF)-κB translocation on TLR4 activation was analyzed using microscopic techniques. Protein and cell cycle analysis was done using Western Blot and FACS respectively.RESULTS The present study shows that TLR4 activation represses HBV infection. As a result of HBV suppression, there are several changes in host factors which include partial release in G1/S cell cycle arrest and changes in host epigenetic marks. Finally, it was observed that anti-viral action of TLR4 takes place through the NF-κB pathway.CONCLUSION The study shows that TLR4 activation in HBV infection brings about changes in hepatocyte microenvironment and can be used for developing a promising therapeutic target in future. 展开更多
关键词 Hepatitis B virus toll like receptor 4 Cell cycle Epigenetic marks Innate immune response
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Toll-like receptor 4-mediated signaling participates in apoptosis of hippocampal neurons 被引量:8
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作者 Yue He Ailing Zhou Wei Jiang 《Neural Regeneration Research》 SCIE CAS CSCD 2013年第29期2744-2753,共10页
The phosphatidylinositol 3 kinase (PI3K)/protein kinase B (AKT) signaling pathway is considered important for cell survival and has been shown to mediate various anti-apoptotic biological effects. This study explo... The phosphatidylinositol 3 kinase (PI3K)/protein kinase B (AKT) signaling pathway is considered important for cell survival and has been shown to mediate various anti-apoptotic biological effects. This study explored the role of the Toll-like receptor 4 (TLR4)-mediated PI3K/AKT-glycogen syn-thase kinase 3β (GSK-3β) signaling pathways in lipopolysaccharide-induced apoptosis in a primary culture of hippocampal neurons. Results demonstrated that the apoptotic ratio of hippocampal neurons stimulated by lipopolysaccharide was significantly higher compared with the control group. Both the expression of P-AKTser473 and P-GSK-3βSserg in hippocampal neurons stimulated by lipopolysaccharide decreased compared with the control, while the level of active Caspase-3 and the ratio of Bax/Bcl-2 were significantly increased. The level of active Caspase-3 and the ratio of Bax/Bcl-2 in hippocampal neurons treated with TLR4 antibody or the GSK-3β inhibitor, LiCl, de-creased before intervention with lipopolysaccharide, but increased after treatment with the AKT in-hibitor, LY294002. These findings suggest that the TLR4-PI3K/AKT-GSKβ signaling pathway may be involved in lipopolysaccharide-induced apoptosis of hippocampal neurons. 展开更多
关键词 neural regeneration brain injury HIPPOCAMPUS neurons toll like receptor 4 phosphatidylinositol 3kinase/protein kinase B-glycogen synthase kinase APOPTOSIS grants-supported paper neu-roregeneration
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Expression and Immune Effect of Toll-Like Receptor 4 in Human Trophoblast Cells 被引量:6
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作者 邓飞涛 韩芳 吴超英 《Journal of Huazhong University of Science and Technology(Medical Sciences)》 SCIE CAS 2009年第3期359-362,共4页
This study investigated the expression and immune effect of TLR4 in human trophoblast cells. The expression level of TLR4 mRNA in normal and LPS-stimulated human term trophoblast cells (1 mg/L LPS, 12 h) was detecte... This study investigated the expression and immune effect of TLR4 in human trophoblast cells. The expression level of TLR4 mRNA in normal and LPS-stimulated human term trophoblast cells (1 mg/L LPS, 12 h) was detected by RT-PCR. In LPS-stimulated human term trophoblast cells of TLR4-blocked group and non-TLR4-blocked group, and normal term trophoblast cells of blank control group, apoptosis rate was measured by flow cytometry (FCM), and the level of TNF-α determined by using enzyme linked immunosorbent assay (ELISA) respectively. RT-PCR results showed that the expression level of TLR4 mRNA in LPS-stimulated human trophoblast cells was significantly higher than that in normal cells (P〈0.01). FCM revealed that there was significant difference in apoptosis rate of LPS-stimulated human term trophoblast cells between TLR4-blocked group and non-TLR4-blocked group (P〈0.05), or between TLR4 antibody-blocked group and blank control group. ELISA indicated that the level of TNF-α in LPS-stimulated human trophoblast cells also had statistical differences between TLR4 antibody-blocked group and non-TLR4 antibody-blocked group (P〈0.05). Our results suggest that TLR4 plays an important role in the immunological mechanism of apoptosis and secretion of TNF-α of human term trophoblast cells stimulated by LPS. 展开更多
关键词 toll like receptor 4 LIPOPOLYSACCHARIDE human trophoblast cells APOPTOSIS TNF-Α
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Betaine inhibits Toll-like receptor 4 expression in rats with ethanol-induced liver injury 被引量:23
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作者 Shi, Qing-Zhao Wang, Lu-Wen +1 位作者 Zhang, Wei Gong, Zuo-Jiong 《World Journal of Gastroenterology》 SCIE CAS CSCD 2010年第7期897-903,共7页
AIM:To test whether ethanol feeding could induce Toll-like receptor 4(TLR4)responses,assess the hepatoprotective effect of betaine and its inhibitive effect on TLR4 in animal models of alcoholic liver injury.METHODS:F... AIM:To test whether ethanol feeding could induce Toll-like receptor 4(TLR4)responses,assess the hepatoprotective effect of betaine and its inhibitive effect on TLR4 in animal models of alcoholic liver injury.METHODS:Forty-eight female Sprague-Dawley rats were randomly divided into four groups as control,model,low and high dose betaine groups.Except control group,all rats were fed with high fat-containing diet plus ethanol and fish oil gavages for 8 wk.Betaine was administered intragastrically after exposure of ethanol for 4 wk.The changes of liver histology were examined.The expression of TLR4 mRNA and protein was detected by RT-PCR and Western blotting,respectively.The serum aminotransferase activity alanine transarninase(ALT),aspartate aminotransferase(AST),serum endotoxin,and liver inflammatory factors tumor necrosis factor-α(TNF-α),interferon-γ(IFN-γ),interleukin-18(IL-18)were also assayed.RESULTS:Compared with control group,rats of model group developed marked liver injury,accompanied by an increase of ALT(159.41±7.74 U/L vs 59.47± 2.34 U/L,P<0.0001),AST(248.25±1.40 U/L vs 116.89±3.48 U/L,P<0.0001),endotoxin(135.37± 30.17 ng/L vs 44.15±7.54 ng/L,P<0.0001),TNF-α(20.81±8.58 pg/mL vs 9.34±2.57 pg/mL,P=0.0003),IFN-γ(30.18±7.60 pg/mL vs 16.86±9.49 pg/mL,P= 0.0039)and IL-18(40.99±8.25 pg/mL vs 19.73±9.31 pg/mL,P=0.0001).At the same time,the expression of TLR4 mRNA and protein was markedly induced in the liver after chronic ethanol consumption(1.45±0.07 vs 0.44±0.04,P<0.0001;1.83±0.13 vs 0.56±0.08,P<0.0001).Compared with model group,betaine feeding resulted in significant decreases of ALT(64.93 ±6.06 U/L vs 159.41±7.74 U/L,P<0.0001),AST(188.73±1.11 U/L vs 248.25±1.40 U/L,P<0.0001),endotoxin(61.80±12.56 ng/L vs 135.37±30.17 ng/L,P<0.0001),TNF-α(9.79±1.32 pg/mL vs 20.81± 8.58 pg/mL,P=0.0003),IFN-γ(18.02±5.96 pg/mL vs 30.18±7.60 pg/mL,P=0.0008)and IL-18(18.23±7.01 pg/mL vs 40.99±8.25 pg/mL,P<0.0001).Betaine also improved liver steatosis.The expression levels of TLR4 mRNA or protein in liver tissues were significantly lowered(0.62±0.04 vs 1.45±0.07,P<0.0001;and 0.65±0.06 vs 1.83±0.13,P<0.0001).There was a statistical difference of TLR4 mRNA and protein expression between high-and low-dose betaine groups(0.62±0.04 vs 0.73±0.05,P<0.0001,and 0.65±0.06 vs 0.81±0.09,P<0.0001).CONCLUSION:Betaine can prevent the alcoholinduced liver injury effectively and improve the liver function.The expression of TLR4 increases significantly in ethanol-fed rats and betaine administration can inhibit TLR4 expression. 展开更多
关键词 BETAINE toll-like receptor 4 Alcoholic liver injury EXPRESSION
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Effects of ω-3 fatty acids on toll-like receptor 4 and nuclear factor-κB p56 in lungs of rats with severe acute pancreatitis 被引量:12
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作者 Bin Wang Xiao-Wei Wu +4 位作者 Mei-Xia Guo Min-Li Li Xiao-Bing Xu Xin-Xin Jin Xiao-Hua Zhang 《World Journal of Gastroenterology》 SCIE CAS 2016年第44期9784-9793,共10页
AIM To determine the effects of ω-3 fatty acids(ω-3FA) on the toll-like receptor 4(TLR4)/nuclear factor κB p56(NF-κBp56) signal pathway in the lungs of rats with severe acute pancreatitis(SAP).METHODS A total of 5... AIM To determine the effects of ω-3 fatty acids(ω-3FA) on the toll-like receptor 4(TLR4)/nuclear factor κB p56(NF-κBp56) signal pathway in the lungs of rats with severe acute pancreatitis(SAP).METHODS A total of 56 Sprague-Dawley rats were randomly divided into 4 groups: control group, SAP-saline group, SAP-soybean oil group and SAP-ω-3FA group. SAP was induced by the retrograde infusion of sodium taurocholate into the pancreatic duct. The expression of TLR4 and NF-κBp56 in the lungs was evaluated by immunohistochemistry and Western blot analysis. The levels of inflammatory cytokines interleukin-6 and tumor necrosis factor-alpha in the lungs were measured by enzyme-linked immunosorbent assay. RESULTS The expression of TLR4 and NF-κBp56 in lungs and of inflammatory cytokines in serum significantly increased in the SAP group compared with the control group(P < 0.05), but was significantly decreased in the ω-3FA group compared with the soybean oil group at 12 and 24 h(P < 0.05).CONCLUSION During the initial stage of SAP, ω-3FA can efficiently lower the inflammatory response and reduce lung injury by triggering the TLR4/NF-κBp56 signal pathway. 展开更多
关键词 Severe acute pancreatitis ω-3 fatty acids Lung injury toll-like receptor 4 Nuclear factor-κB p56 CYTOKINE
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Association of Toll-like receptor 4 Signaling Pathway with Steroid-induced Femoral Head Osteonecrosis in Rats 被引量:10
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作者 田雷 周东生 +4 位作者 王坤正 张伟 时志斌 樊立宏 孙水 《Journal of Huazhong University of Science and Technology(Medical Sciences)》 SCIE CAS 2014年第5期679-686,共8页
Osteonecrosis of the femoral head is frequently observed in patients treated with excessive corticosteroids. However, the pathogenesis of corticosteroid-induced osteonecrosis remains unclear. The purpose of this study... Osteonecrosis of the femoral head is frequently observed in patients treated with excessive corticosteroids. However, the pathogenesis of corticosteroid-induced osteonecrosis remains unclear. The purpose of this study was to investigate the role of Toil-like receptor 4 (TLR4) signaling pathway in steroid-induced femoral head osteonecrosis in rats. Male Sprague-Dawley rats were injected intramus- cularly with 20 mg/kg methylprednisolone (MP) for 8 weeks, twice per week. The animals were sacri- ficed at 2, 4 and 8 weeks after the last MP injection, respectively, and then allocated to the 2-, 4- and 8-week model groups (n=24 each). Rats in the control group (n=12) were not given any treatment. Histopathological analysis was performed and the concentration of tartrate-resistant acid phosphatase (TRAP) in plasma was determined. The activation of osteoclasts in the femoral head was assessed by TRAP staining. The expression of TLR4, MyD88, TRAF6 and NF-Id3 p65 that are involved in TLR4 signaling, and MCP-1 production were detected by using real-time PCR (RT-PCR) and Western blotting. The results showed that the osteonecrosis in the femoral head was clearly observed and the concentra- tion of TRAP in the plasma was increased in the model rats. The femoral head tissues in MP-treated rats were positive for TRAP and the intensity of TRAP staining was greater in MP-treated rats than in con- trol rats. As compared with the control group, the mRNA expression of TLR4 signaling-related factors was enhanced significantly at 4 and 8 weeks, and the protein levels of these factors increased signifi- cantly with time. It was concluded that MP could induce the femoral head osteonecrosis in rats, which was associated with osteoclast activation via the TLR4 signaling pathway. These findings suggest that TLR4 signaling pathway plays a pivotal role in the pathogenesis of steroid-induced osteonecrosis. 展开更多
关键词 OSTEONECROSIS toll-like receptor 4 CORTICOSTEROIDS femoral head RAT
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Starring role of toll-like receptor-4 activation in the gutliver axis 被引量:11
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作者 Simone Carotti Michele Pier Luca Guarino +1 位作者 Umberto Vespasiani-Gentilucci Sergio Morini 《World Journal of Gastrointestinal Pathophysiology》 CAS 2015年第4期99-109,共11页
Since the introduction of the term "gut-liver axis", many studies have focused on the functional links of intestinal microbiota, barrier function and immune responses to liver physiology. Intestinal and extr... Since the introduction of the term "gut-liver axis", many studies have focused on the functional links of intestinal microbiota, barrier function and immune responses to liver physiology. Intestinal and extra-intestinal diseases alter microbiota composition and lead to dysbiosis, which aggravates impaired intestinal barrier function via increased lipopolysaccharide translocation. The subsequent increased passage of gut-derived product from the intestinal lumen to the organ wall and bloodstream affects gut motility and liver biology. The activation of the toll-like receptor 4(TLR-4) likely plays a key role in both cases. This review analyzed the most recent literature on the gut-liver axis, with a particular focus on the role of TLR-4 activation. Findings that linked liver disease with dysbiosis are evaluated, and links between dysbiosis and alterations of intestinal permeability and motility are discussed. We also examine the mechanisms of translocated gut bacteria and/or the bacterial product activation of liver inflammation and fibrogenesis via activity on different hepatic cell types. 展开更多
关键词 GUT MICROBIOTA DYSBIOSIS toll-like receptor 4 GUT
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Effects of Propofol on The mRNA Expression of Toll-like Receptor 4 in BV-2 Cells During Mimic Ischemia-Reperfusion Injury In Vitro 被引量:7
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作者 张清 孙鹏 +2 位作者 张诗海 田元 张景辉 《Journal of Huazhong University of Science and Technology(Medical Sciences)》 SCIE CAS 2008年第6期711-713,共3页
This study investigated the effects of propofol on the mRNA expression of Toll-like receptor-4 (TLR4) in BV-2 cells during mimic ischemia-reperfusion (I/R) injury in vitro. BV-2 cells, a mouse microglia line, were... This study investigated the effects of propofol on the mRNA expression of Toll-like receptor-4 (TLR4) in BV-2 cells during mimic ischemia-reperfusion (I/R) injury in vitro. BV-2 cells, a mouse microglia line, were cultured and divided into 4 groups at random: control group (group C), ischemia/reperfusion group (group I/R), low-dose propofol (25 μmol/L) intervention group (group PF25) and high-dose propofol (100 μmol/L) intervention group (group PF100). The mRNA expression of TLR4 and NF-κB was measured by means of RT-PCR. TNF-α levels in the supernatants of BV-2 cells were detected by ELISA. The results showed that the mRNA expression of TLR4 and NF-κB was significantly higher in groups I/R, PF25 and PF100 than in group C (P〈0.01). And the TNF-α level in the supernatants was elevated in groups I/R, PF25 and PF100 as compared with that in group C (P〈0.01). After pre-treatment with propofol, the mRNA expressions of TLR4 and NF-κB and the TNF-α level were significantly decreased in groups PF25 and PF100 in comparison to those in group I/R (P〈0.01). And the decrease in those indicators was more significant in group PF100 than in group PF25 (P〈0.01). It was concluded that propofol exerted brain-protecting effects during I/R injury by suppressing the mRNA expressions of TLR4 and NF-κB and deceasing the TNF-α level. 展开更多
关键词 PROPOFOL toll-like receptor-4 ISCHEMIA/REPERFUSION MICROGLIA
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Production of interleukin-1β related to mammalian target of rapamycin/Toll-like receptor 4 signaling pathway during Aspergillus fumigatus infection of the mouse cornea 被引量:6
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作者 Rui Xu Jing Lin +4 位作者 Gui-Qiu Zhao Cui Li Cheng-Ye Che Qiang Xu Min Liu 《International Journal of Ophthalmology(English edition)》 SCIE CAS 2018年第5期712-718,共7页
AIM:To elucidate the effect of rapamycin on regulating the production of interleukin(IL)-1β in Aspergillus fumigatus(A.fumigatus)-induced keratitis and to verify whether the expression of IL-1β in A.fumigatus k... AIM:To elucidate the effect of rapamycin on regulating the production of interleukin(IL)-1β in Aspergillus fumigatus(A.fumigatus)-induced keratitis and to verify whether the expression of IL-1β in A.fumigatus keratitis is associated with the mammalian target of rapamycin(mT OR)/Toll-like receptor 4(TLR4) signaling pathway.METHODS:Fungal keratitis mouse models of susceptible C57 BL/6 mice were established using A.fumigatus.The mice were subsequently treated with rapamycin.The protein levels of p-mT OR,TLR4,and IL-1β in normal and infected corneal tissue were measured by Western blot.The TLR4 and IL-1β m RNA levels were determined by real-time polymerase chain reaction(PCR).RESULTS:In C57 BL/6 mice,rapamycin treatment decreased the clinical scores and production of the pro-inflammatory cytokine,IL-1β.The expression of TLR4,stimulated by A.fumigatus,was reduced as well when the mT OR signaling pathway was suppressed by rapamycin.CONCLUSION:Rapamycin is beneficial for the outcome of fungal keratitis and has an inhibitory effect expression of the inflammatory cytokine IL-1β.The inhibitory effect on IL-1β expression can be associated with the mT OR/TLR4 signaling pathway in A.fumigatus infection in mice. 展开更多
关键词 KERATITIS INTERLEUKIN-1Β mammalian target of rapamycin toll-like receptor 4 mice
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Impact of Probiotics on Toll-like Receptor 4 Expression in an Experimental Model of Ulcerative Colitis 被引量:6
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作者 杨霞 付妤 +1 位作者 刘俊 任宏宇 《Journal of Huazhong University of Science and Technology(Medical Sciences)》 SCIE CAS 2013年第5期661-665,共5页
Toll-like receptors (TLRs) are key components of the innate immune system which trigger antimicrobial host defense responses. This study aimed to investigate the impact of probiotics (Lactoba- cillus, Bifiidobacter... Toll-like receptors (TLRs) are key components of the innate immune system which trigger antimicrobial host defense responses. This study aimed to investigate the impact of probiotics (Lactoba- cillus, Bifiidobacterium) on the expression of TLR4 and tumor necrosis factor-alpha (TNF-α in the co- lon mucosa of rat experimental ulcerative colitis model induced by trinitrobenzene sulfonic acid (TNBS)/ethanol and immune complexes. The gross and histological changes of the colonic mucosa were observed and assessed by the means-standard deviation and independent samples t-test. The pro- tein expression levels of TLR4 and TNF-α were detected by using immunohistochemistry and Westem blotting, respectively. It was revealed that there was visible infiltration of inflammatory cells, formation of crypt abscess, and the reduction of goblet cells in the colon tissue of experimental models. As com- pared with the control group, the levels of TLR4 and TNF-α protein were significantly increased in the model group (P〈0.01 for both). No significant difference was found in the expression of TLR4 and TNF-α between the two-week probiotics treatment group and the model group (P〉0.05), whereas sig- nificant reductions were shown in rats which were treated with probiotics for four weeks as compared with the model group (P〈0.01). There was no significant difference between two probiotics-treated groups. Our results implied that probiotics were likely to play a key role in protecting ulcerative colitis by reducing the inflammatory factor TNF-α expression through inhibiting the TLR4 expression in the colon tissue of experimental models. 展开更多
关键词 ulcerative colitis animal model toll-like receptor 4 tumor necrosis factor-a trinitroben-zene sulfonic acid
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A 5'-flanking region polymorphism in toll-like receptor 4 is associated with gastric cancer in a Chinese population 被引量:5
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作者 Hua Huang Juan Wu +9 位作者 Guangfu Jin Hanze Zhang Yanbing Ding Zhaolai Hua Yan Zhou Yan Xue Yan Lu Zhibin Hu Yaochu Xu Hongbing Shen 《The Journal of Biomedical Research》 CAS 2010年第2期100-106,共7页
Objective: Inflammation induced by H.pylori colonization in the stomach is related to the development of gastric cancer and the genetic variations of the genes involved in the immune responses modify the host respons... Objective: Inflammation induced by H.pylori colonization in the stomach is related to the development of gastric cancer and the genetic variations of the genes involved in the immune responses modify the host response to the infection. The aim of this study was to evaluate whether polymorphisms in the toll-like receptor 4 (TLR4) gene, a key regulator of both innate and adaptive immunity, were related to the susceptibility to 展开更多
关键词 toll-like receptor 4 POLYMORPHISMS SUSCEPTIBILITY gastric cancer
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Mechanisms of Increased Expression of Toll-Like Receptor-4 in Human Monocyte/Macrophage-derived Foam Cells 被引量:5
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作者 成蓓 余其振 +2 位作者 白智峰 柯丽 何平 《Journal of Huazhong University of Science and Technology(Medical Sciences)》 SCIE CAS 2005年第5期477-479,共3页
Summary: The mechanisms of increased expression of toll-like receptor 4 (TLR-4) during the formation of foam cells were explored. Low density lipoprotein (LDL) was prepared by density gradient ultracentrifugation... Summary: The mechanisms of increased expression of toll-like receptor 4 (TLR-4) during the formation of foam cells were explored. Low density lipoprotein (LDL) was prepared by density gradient ultracentrifugation and oxidized by incubation with CuClz. The human monocytic leukemia cell line (THP-1) was cultured in RPMI1640. The differentiation of THP-1 cells into macrophages (MPs) was induced by using myristate acetate (PMA) for 48 h. The macrophages were then incubated with oxidized LDL (ox-LDL) to generate foam cells (FCs). The mRNA and protein expression levels of human TLR-4 were detected by immunocytochemistry, Western blotting and reverse transcription polymerase chain reaction (RT-PCR). The results showed that the TLR-4 mRNA and the protein expression levels were significantly increased during the differentiation of monocytes into macrophages (P〈0. 05) as well as during the formation of lipid-laden foam cells (P〈0.05). It was concluded that the upregulation of human TLR-4 gene expression during the differentiation of monocytes into macrophages and the differentiation of macrophages into foam cells could increase TLR-4 protein synthesis dramatically, which may enhance the ability of foam cells inflammation reaction in atherosclerosis. 展开更多
关键词 toll-like receptor 4 MACROPHAGES ARTERIOSCLEROSIS
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Toll-like receptor 4 polymorphisms and bacterial infections in patients with cirrhosis and ascites 被引量:3
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作者 Edilmar Alvarado-Tapias Carlos Guarner-Argente +11 位作者 Elida Oblitas Elisabet Sánchez Silvia Vidal Eva Román Mar Concepción Maria Poca Cristina Gely Oana Pavel Juan Camilo Nieto Cándido Juárez Carlos Guarner Germán Soriano 《World Journal of Hepatology》 CAS 2018年第1期124-133,共10页
AIM To assess the relationship between the presence of toll-like receptor 4(TLR4) polymorphisms and bacterial infections in cirrhotic patients with ascites. METHODS We prospectively included consecutive patients with ... AIM To assess the relationship between the presence of toll-like receptor 4(TLR4) polymorphisms and bacterial infections in cirrhotic patients with ascites. METHODS We prospectively included consecutive patients with cirrhosis and ascites hospitalized during a 6-year period. Patients with human immunodeficiency virus(HIV) infection or any other immunodeficiency, patients with advanced hepatocellular carcinoma(beyond Milan's criteria) or any other condition determining poor short-term prognosis, and patients with a permanent urinary catheter were excluded. The presence of D299 G and/or T399 I TLR4 polymorphisms was determined by sequencing and related to the incidence and probability of bacterial infections, other complications of cirrhosis, hepatocellular carcinoma, and mortality during follow-up. A multivariate analysis to identify predictive variables of mortality in the whole series was performed. RESULTS We included 258 patients: 28(10.8%) were carriers of D299G and/or T399I TLR4 polymorphisms(polymorphism group) and 230 patients were not(wildtype group). The probability of developing any bacterial infection at one-year follow-up was 78% in the polymorphism group and 69% in the wild-type group(P = 0.54). The one-year probability of presenting infections caused by gram-negative bacilli(51% vs 44%, P = 0.68), infections caused by gram-positive cocci(49% vs 40%, P = 0.53), and spontaneous bacterial peritonitis(29% vs 34%, respectively, P = 0.99) did not differ between the two groups. The oneyear probability of transplant-free survival was 55% in the polymorphism group and 66% in the wild-type group(P = 0.15). Multivariate analysis confirmed that age, Child-Pugh score, active alcohol intake, previous hepatic encephalopathy, hepatocellular carcinoma and serum creatinine were associated with a higher risk of death during follow-up. CONCLUSION Genetic polymorphisms D299 G and/or T399 I of TLR4 do not seem to play a relevant role in the predisposition of cirrhotic patients with ascites to bacterial infections. 展开更多
关键词 CIRRHOSIS Genetic POLYMORPHISMS toll-like receptor 4 BACTERIAL INFECTIONS ASCITES
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Role of Toll-like receptor 4 in inflammatory reactions of hippocampal neurons 被引量:3
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作者 Yae Hu Jiahui Mao +1 位作者 Yu Zhang Ailing Zhou 《Neural Regeneration Research》 SCIE CAS CSCD 2013年第16期1465-1472,共8页
Lipopolysaccharide stimulates Toll-like receptor 4 on immune cells to produce immune mediators. Toll-like receptor 4 is also expressed by non-immune cells, which can be stimulated by lipopolysaccharide. However, wheth... Lipopolysaccharide stimulates Toll-like receptor 4 on immune cells to produce immune mediators. Toll-like receptor 4 is also expressed by non-immune cells, which can be stimulated by lipopolysaccharide. However, whether Toll-like receptor 4 is expressed by primary cultured hippocampal neurons and its specific role in lipopolysaccharide-induced neuroinflammation is currently undefined, in this study, Toll-like receptor 4 antibody blocking was used to analyze the Toll-like receptor 4 signaling pathway and changes in inflammation of lipopolysaccharide stimulated hippocampal neurons. Immunofluorescence showed that Toll-like receptor 4 protein was mainly located in the membrane of hippocampal neurons. Quantitative reverse transcription-PCR and western blot assay showed that after stimulation of lipopolysaccharide, the mRNA and protein levels of Toll-like receptor 4 and the mRNA levels of interleukin-ll3 and tumor necrosis factor-(] were significantly increased. In addition, there was increased phosphorylation and degradation of kappa B a inhibitor in the cytosol and increased nuclear factor-KB p65 expression in the nuclei. Pretreatment with Toll-like receptor 4 antibody could almost completely block this increase. These experimental findings indicate that lipopolysaccharide participates in neuroinflammation by stimulating Toll-like receptor 4/nuclear factor-KB pathway in hippocampal neurons, which may be both "passive victims" and "activators" of neuroinflammation. 展开更多
关键词 neural regeneration inflammation toll-like receptor 4 LIPOPOLYSACCHARIDE nuclear factor-kappa B interleukin-1 beta tumor necrosis factor-alpha HIPPOCAMPUS neurons grants-supported paper NEUROREGENERATION
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Impact of Toll-like Receptor 4 Deficiency on Cerebrocardiac Syndrome 被引量:3
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作者 孙鹏 徐丽 +1 位作者 张清 李倩 《Journal of Huazhong University of Science and Technology(Medical Sciences)》 SCIE CAS 2014年第2期161-164,共4页
In order to investigate the role of Toll-like receptor 4 (TLR4) in cerebrocardiac syndrome (CCS), the partial cerebral ischemia/reperfusion (I/R) models in mice with different TLR4 genotypes were established in ... In order to investigate the role of Toll-like receptor 4 (TLR4) in cerebrocardiac syndrome (CCS), the partial cerebral ischemia/reperfusion (I/R) models in mice with different TLR4 genotypes were established in the present study. TLR4 wild-type (C3H/HeN) and mutant (C3H/HeJ) mice of 6-8 weeks of age were divided into 4 groups at random: C3H/HeN sham group (n=10), C3H/HeJ sham group (n=10), C3H/HeN model group (n=10) and C3H/HeJ model group (n=10). Partial cerebral I/R was caused by the middle cerebral artery occlusion (MCAO) to duplicate CCS models in mice. After the operation, the electrocardiogram (ECG), the level of tumor necrosis factor-alpha (TNF-c0 in myocardial tissue and the cardiac pathological changes were observed in each group. It was shown that the brain infarct volume in C3H/HeN model group was larger than that in C3H/HeJ model group (P〈0.01). The ST segment change and T wave inversion occurred frequently in model groups. Moreover, the TNF-ct level in C3H/HeN model group was higher than that in C3H/HeJ model group (P〈0.01). The myocar- dial injury was aggravated in C3H/HeN group as compared with C3H/HeJ group. It was concluded that TLR4 was implicated in the development of CCS. 展开更多
关键词 cerebrocardiac syndrome toll-like receptor 4 myocardial tissue electron microscope
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Toll-like receptor 4 as a possible therapeutic target for delayed brain injuries after aneurysmal subarachnoid hemorrhage 被引量:25
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作者 Takeshi Okada Hidenori Suzuki 《Neural Regeneration Research》 SCIE CAS CSCD 2017年第2期193-196,共4页
Neuroinflammation is a well-recognized consequence of subarachnoid hemorrhage(SAH), and Toll-like receptor(TLR) 4 may be an important therapeutic target for post-SAH neuroinflammation. Of the TLR family members, T... Neuroinflammation is a well-recognized consequence of subarachnoid hemorrhage(SAH), and Toll-like receptor(TLR) 4 may be an important therapeutic target for post-SAH neuroinflammation. Of the TLR family members, TLR4 is expressed in various cell types in the central nervous system, and is unique in that it can signal through both the myeloid differentiation primary-response protein 88-dependent and the toll receptor associated activator of interferon-dependent cascades to coordinate the maximal inflammatory response. TLR4 can be activated by many endogenous ligands having damage-associated molecular patterns including heme and fibrinogen at the rupture of an intracranial aneurysm, and the resultant inflammatory reaction and thereby tissue damages may furthermore activate TLR4. It is widely accepted that the excreted products of TLR4 signaling alter neuronal functions. Previous studies have focused on the pathway through nuclear factor(NF)-κΒ signaling among TLR4 signaling pathways as to the development of early brain injury(EBI) such as neuronal apoptosis and blood-brain barrier disruption, and cerebral vasospasm. However, many findings suggest that both pathways via NF-κΒ and mitogen-activated protein kinases may be involved in EBI and cerebral vasospasm development. To overcome EBI and cerebral vasospasm is important to improve outcomes after SAH, because both EBI and vasopasm are responsible for delayed brain injuries or delayed cerebral ischemia, the most important preventable cause of poor outcomes after SAH. Increasing evidence has shown that TLR4 signaling plays an important role in SAH-induced brain injuries. Better understanding of the roles of TLR4 signaling in SAH will facilitate development of new treatments. 展开更多
关键词 cerebral aneurysm cerebral vasospasm early brain injury delayed brain injury delayed cerebral ischemia inflammation subarachnoid hemorrhage toll-like receptor 4
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Expression of Toll-like Receptor 4 in Neonatal Cord Blood Mononuclear Cells in Patients with Preeclampsia 被引量:2
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作者 夏革清 徐丹芬 +1 位作者 吴敏 吴超英 《Journal of Huazhong University of Science and Technology(Medical Sciences)》 SCIE CAS 2010年第5期615-619,共5页
The expression of Toll-like receptor 4 (TLR4) in neonatal cord blood mononuclear cells (MNCs) and serum TNF-α were investigated in order to explore the roles of TLR4 in the pathogenesis of preeclampsia.The study enro... The expression of Toll-like receptor 4 (TLR4) in neonatal cord blood mononuclear cells (MNCs) and serum TNF-α were investigated in order to explore the roles of TLR4 in the pathogenesis of preeclampsia.The study enrolled 27 patients suffering from preeclampsia (experimental group) and 21 normal pregnancy patients (control group).After MNCs were separated, the expression of TLR4 mRNA and protein was detected by using real-time quantitative PCR and Western blotting respectively, and the expression of TNF-α by using ELISA.The results showed the TLR4 mRNA level in cord blood MNCs (2-CT:0.07±0.17), TLR4 protein expression level (absorbance ratio:0.81%±0.15%) and TNF-α level (9.5±1.73 pg/mL) were all increased in experimental group as compared with control group with the differences being statistically significant (P【0.05).There was a positive correlation between the expression of TLR4 mRNA and TNF-α in both experimental group and control group (r=0.54 and 0.53, respectively, P【0.05).It was concluded that TLR4 expression in the experimental group of cord blood MNCs was increased and there was a positive correlation between the expression of TLR4 mRNA and TNF-α in both groups.TLR4-mediated release of inflammatory cytokines may be one of the important reasons leading to preeclampsia. 展开更多
关键词 PREECLAMPSIA mononuclear cells toll-like receptor 4 tumor necrosis factor α
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Role of Toll-like receptor 4 and Janus kinase and signal transducer and activator of transcription signal transduction pathway in sepsis-induced brain damage 被引量:1
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作者 Haiyan Yin Jianrui Wei +2 位作者 Rui Zhang Xiaoling Ye Youfeng Zhu 《Neural Regeneration Research》 SCIE CAS CSCD 2011年第32期2511-2515,共5页
The Janus kinase and signal transducer and activator of transcription (JAK/STAT) signal transduction pathway is involved in sepsis-induced functional damage to the heart, liver, kidney, and other organs. However, th... The Janus kinase and signal transducer and activator of transcription (JAK/STAT) signal transduction pathway is involved in sepsis-induced functional damage to the heart, liver, kidney, and other organs. However, the cellular and molecular mechanisms underlying sepsis-induced brain damage remain elusive. In the present study, we found severe loss of neurons in the hippocampal CA1 region in rats with sepsis-induced brain damage following intraperitoneal injection of endotoxin, The expression of toll-like receptor 4, tumor necrosis factor a, and interleukin-6 was significantly increased in brain tissues following lipopolysaccharide exposure. AG490 (JAK2 antagonist) and rapamycin (STAT3 antagonist) significantly reduced neuronal loss and suppressed the increased expression of toll-like receptor 4, tumor necrosis factor a, and interleukin-6 in the hippocampal CA1 region in sepsis-induced brain damaged rats. Overall, these data suggest that blockade of the JAK/STAT signal transduction pathway is neuroprotective in sepsis-induced brain damage via the inhibition of toll-like receptor 4, tumor necrosis factor a, and interleukin-6 exoression. 展开更多
关键词 brain damage Janus kinase and signal transducer and activator of transcription SEPSIS signal transduction pathway toll-like receptor 4
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Transforming growth factor-β and toll-like receptor-4 polymorphisms are not associated with fibrosis in haemochromatosis 被引量:1
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作者 Marnie J Wood Lawrie W Powell +2 位作者 Jeannette L Dixon V Nathan Subramaniam Grant A Ramm 《World Journal of Gastroenterology》 SCIE CAS 2013年第48期9366-9376,共11页
AIM:To investigate the role of genetic polymorphisms in the progression of hepatic fibrosis in hereditary haemochromatosis.METHODS:A cohort of 245 well-characterised C282Y homozygous patients with haemochromatosis was... AIM:To investigate the role of genetic polymorphisms in the progression of hepatic fibrosis in hereditary haemochromatosis.METHODS:A cohort of 245 well-characterised C282Y homozygous patients with haemochromatosis was studied,with all subjects having liver biopsy data and DNA available for testing.This study assessed the association of eight single nucleotide polymorphisms(SNPs)in a total of six genes including toll-like receptor 4(TLR4),transforming growth factor-beta(TGF-β),oxoguanine DNA glycosylase,monocyte chemoattractant protein 1,chemokine C-C motif receptor 2 and interleukin-10 with liver disease severity.Genotyping was performed using high resolution melt analysis and sequencing.The results were analysed in relation to the stage of hepatic fibrosis in multivariate analysis incorporating other cofactors including alcohol consumption and hepatic iron concentration.RESULTS:There were significant associations between the cofactors of male gender(P=0.0001),increasing age(P=0.006),alcohol consumption(P=0.0001),steatosis(P=0.03),hepatic iron concentration(P<0.0001)and the presence of hepatic fibrosis.Of the candidate gene polymorphisms studied,none showed a significant association with hepatic fibrosis in univariate or multivariate analysis incorporating cofactors.We also specifically studied patients with hepatic iron loading above threshold levels for cirrhosis and compared the genetic polymorphisms between those with no fibrosis vs cirrhosis however there was no significant effect from any of the candidate genes studied.Importantly,in this large,well characterised cohort of patients there was no association between SNPs for TGF-βor TLR4and the presence of fibrosis,cirrhosis or increasing fibrosis stage in multivariate analysis.CONCLUSION:In our large,well characterised group of haemochromatosis subjects we did not demonstrate any relationship between candidate gene polymorphisms and hepatic fibrosis or cirrhosis. 展开更多
关键词 HAEMOCHROMATOSIS Genetic polymorphism Liver FIBROSIS toll-like receptor 4 Interleukin 10 Monocyte CHEMOATTRACTANT protein 1 Chemokine(C-C motif) ligand 2 Transforming growth factor beta 8-oxoguanine DNA GLYCOSYLASE
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Microglia activation mediated by toll-like receptor-4 impairs brain white matter tracts in rats 被引量:4
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作者 Xinglong Yang Jingdong Zhang +3 位作者 Lian Duan Huangui Xiong Yanping Jiang Houcheng Liang 《The Journal of Biomedical Research》 CAS CSCD 2018年第2期136-144,共9页
Microglia activation and white matter injury coexist after repeated episodes of mild brain trauma and ischemic stroke. Axon degeneration and demyelination can activate microglia; however, it is unclear whether early m... Microglia activation and white matter injury coexist after repeated episodes of mild brain trauma and ischemic stroke. Axon degeneration and demyelination can activate microglia; however, it is unclear whether early microglia activation can impair the function of white matter tracts and lead to injury. Rat corpus callosum(CC) slices were treated with lipopolysaccharide(LPS) or LPS + Rhodobacter sphaeroides(RS)-LPS that is a toll-like receptor 4(TLR-4) antagonist. Functional changes reflected by the change of axon compound action potentials(CAPs) and the accumulation of β-amyloid precursor protein(β-APP) in CC nerve fibers. Microglia activation was monitored by ionized calcium binding adaptor-1 immunofluorescent stain, based on well-established morphological criteria and paralleled proportional area measurement. Input-output(I/O) curves of CAPs in response to increased stimuli were significantly downshifted in a dose-dependent manner in LPS(0.2, 0.5 and 1.0μg/mL)-treated slices, implying that axons neurophysiological function was undermined. LPS caused significant β-APP accumulation in CC tissues,reflecting the deterioration of fast axon transport. LPS-induced I/O curve downshift and P-APP accumulation were significantly reversed by the pre-treatment or co-incubation with RS-LPS. RS-LPS alone did not change the I/O curve.The degree of malfunction was correlated with microglia activation, as was shown by the measurements of proportional areas. Function of CC nerve fibers was evidently impaired by microglia activation and reversed by a TLP-4 antagonist, suggesting that the TLP-4 pathway lead to microglia activation. 展开更多
关键词 lipopolysaccharide Rhodobacter sphaeroides toll-like receptor 4 microglia activation white matter tract malfunction
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