Significance Of Toll-like Receptor Research Articles

A Review: The Significance of Toll-Like Receptors 2 and 4, and NF-κB Signaling in Endothelial Cells during Atherosclerosis.

Atherosclerosis (AS) is a chronic inflammatory vascular disease that begins with endothelial activation followed by a series of inflammatory responses, plaque formation, and finally rupture. An early event in endothelial dysfunction is activation of the nuclear factor-κB (NF-κB) signaling axis. Toll-like receptors (TLRs) in endothelial cells (ECs) play an essential role in recognizing pathogen-associated molecular patterns (PAMPs), damage-associated molecular patterns (DAMPs), and lifestyle-associated molecular patterns (LAMPs). Activation of the canonical NF-κB pathway stimulates the expression of cytokines, chemokines, and an array of additional genes which activate and amplify AS-associated inflammatory responses. In this review, we discuss the involvement of TLR2/4 and NF-κB signaling in ECs during AS initiation, as well as regulation of the inflammatory response during AS by noncoding RNAs, especially microRNA (miRNA) and circular RNA (circRNA).

Toll-Like Receptors in Stem/Progenitor Cells.

One of the bridges that control the cross-talk between the innate and adaptive immune systems is toll-like receptors (TLRs). TLRs interact with molecules shared and maintained by the source pathogens, but also with endogenous molecules derived from injured tissues (damage/danger-associated molecular patterns - DAMPs). This is likely why some kinds of stem/progenitor cells (SCs) have been found to express TLRs. The role of TLRs in regulating basal motility, proliferation, processes of differentiation, self-renewal, and immunomodulation has been demonstrated in these cells. In this book chapter, we will discuss the many different functions assumed by the TLRs in SCs, pointing out that, depending on the context and the type of ligands they perceive, they may have different effects. In addition, the role of TLR in SC's response to specific tissue damage and in reparative processes will be addressed, as well as how the discovery of molecules mediating TLR signaling's differential function may be decisive for the development of new therapeutic strategies. Given the available studies on TLRs in SCs, the significance of TLRs in sensing an injury to stem/progenitor cells and evaluating their action and reparative activity, which depends on the circumstances, will be discussed here. It could also be possible that SCs used in therapy could theoretically be exposed to TLR ligands, which could modulate their in vivo therapeutic potential. In this context, we need to better understand the mechanisms of action of TLRs on SCs and learn how to regulate these receptors and their downstream pathways in a precise way in order to modulate SC proliferation, survival, migration, and differentiation in the pathological environment. In this way, cell therapy may be strengthened and made safer in the future.

Expression and significance of Toll-like receptor 4 in renal tissue and peripheral blood of children with idiopathic nephrotic syndrome

Objective To investigate the expression and significance of Toll-like receptor 4 (TLR4) in renal tissue and peripheral blood of children with idiopathic nephrotic syndrome(INS). Methods The renal biopsy tissues of 78 children with INS diagnosed in the First Affiliated Hospital of Xinxiang Medical University from October 2015 to June 2018 and normal renal tissues of 21 children (control group 1) were collected, and the expressions of TLR4 in the renal tissue was detected by using immunohistochemical method.The expression of TLR4 in different renal pathological types and clinical types of INS was compared, and the correlation of TLR4 with 24-hour urinary protein and serum albumin was analyzed.The expression levels of TLR4 in peripheral blood of children with INS before and after treatment (active stage and remission stage) and 23 healthy children (control group 2) were detected by enzyme linked immunosorbent assay(ELISA). The serum expression levels of TLR4 in different renal pathological types and clinical types of INS were compared, and the correlation of TLR4 with 24-hour urinary protein and serum albumin was analyzed; The correlation between TLR4 expression in renal tubules and in the serum of children with INS was also analyzed. Results (1)Compared with the expression of TLR4 in normal renal tissues[(0.93±0.26)%], the expression of TLR4 in glomeruli and interstitium of all pathological types of INS [mesangial proliferative glomerulonephritis (MsPGN): (0.93 ± 0.21)%, focal segmental glomerulosclerosis (FSGS): (1.02±0.25)%, membranous glomerulonephritis(MN): (1.03±0.09)%, minimal change disease(MCD): (1.02±0.27)%]was not significantly different (F=0.741, P=0.562), but the expression of TLR4 in renal tubules[MCD: (82.94±4.62)%, MN: (63.54±1.98)%, MsPGN(42.32±2.97)%, FSGS: (22.60±2.07)%] was significantly increased (F=1 929.842, P<0.01), Especially, the expression of TLR4 in renal tubules of MCD type INS was significantly higher than that of MN, MsPG N and FSGS [MCD: (82.94±4.62)%, MN: (63.54±1.98)%, MsPGN: (42.32±2.97)%, FSGS: (22.60±2.07)%], and the differences were statistically significant(all P<0.01). TLR4 expression in renal tubules was the highest in steroid-sensitive nephrotic syndrome (SSNS) type and the lowest in INS patients with steroid-resistant nephrotic syndrome (SRNS) type, and the differences were statistically significant(F=220.951, P<0.01). (2)The expression of serum TLR4 in INS children at the active stage [MsPNG: (143.36±12.99) ng/L, FSGS(75.94±7.29) ng/L, MN(210.22±14.66) ng/L, MCD(283.93±21.58) ng/L]was significantly higher than that in INS children at remission stage [MsPNG: (29.51±4.93) ng/L, FSGS(15.66±3.78) ng/L, MN(45.40±5.73) ng/L, MCD(62.29±7.90) ng/L]and control group 2[(0.69 ± 0.33) ng/L], and the differences were statistically significant(all P<0.01); the expression of serum TLR4 in INS children at remission stage was significantly higher than that in the control group 2 (F=286.287, P<0.01). TLR4 had the highest expression level in serum of MCD type INS children at active and remission stages, followed by MN and FSGS successively.The expression of serum TLR4 was highest in SSNS and lowest in SRNS, and the differences were statistically significant (F=147.438, P<0.01). (3)The expression of TLR4 in renal tubules of children with INS[(62.82 ±20.94)%]was positively correlated with the expression of TLR4 in serum[(213.26±73.33) ng/L] (r=0.852, P< 0.05). The expression levels of TLR4 in renal tubules and serum of INS patients at active stage were positively correlated with 24-hour urinary protein level[(123.05±33.55) mg/kg] (r=0.401, 0.427, all P<0.05), and negatively correlated with serum albumin level[(19.54±3.55)g/L] (r=-0.602, -0.617, all P<0.05). Conclusions The expression of TLR4 in renal tubules and serum of children with INS increases, and may be related to different renal pathological types and clinical types of children with INS, as well as disease activity. Key words: Toll-like receptor 4; Kidney tissue; Serum; Idiopathic nephrotic syndrome; Child

The significance of Toll-like receptors in selected nephropathies

The diseases associated with kidney damage are an increasingly common problem in modern society and complications of chronic renal failure can result in death. Research conducted by many scientific centers, both Polish and foreign, concern the search for possible factors involved in the pathogenesis of glomerulonephritis. One of the possible causes of nephropathy may include the dysfunction of Toll-like receptors (TLRs), which constitute a “bridge” between innate and acquired response. TLRs are involved in receiving signals related to pathogen associated molecular patterns (PAMPs) as well as receiving information related to the danger associated molecular patterns (DAMP). The stimulation of these receptors activates a cascade of reactions in the course of which various mediators, including pro-inflammatory mediators, are produced. The resulting long-lasting inflammation that develops within the glomerulus may cause kidney damage. In both nephropathies caused by excessive production of antibodies in the IgA class, as well as nephropathy induced by diabetes or lupus, the expression of individual TLRs may indicate an inducer of an inflammatory reaction cascade that leads to kidney damage. This article focuses on literature reports that present current views on the role of TLRs in the pathogenesis of the most common nephropathies.

Expressions and significance of Toll-like receptor 3 and Toll-like receptor 4 in renal tissues and peripheral blood mononuclear cells in childhood primary IgA nephropathy

Objective To investigate the expressions and clinical significance of Toll like receptor (TLR) 3 and TLR4 in peripheral blood mononuclear cells and renal tissues of children with primary IgA nephropathy. Methods A total of 34 children with primary IgA nephropathy were selected as the IgA nephropathy group, who were confirmed by renal biopsy, from the Department of Pediatrics, the First Affiliated Hospital of Xinxiang Medical University, from September 2014 to June 2016.In the same period, 7 cases of renal tumor who underwent nephrectomy in Pediatric Surgery became control group A, and 10 cases of healthy children became control group B, and the expressions of TLR3 and TLR4 in renal tissue were detected by adopting immunohistochemistry between IgA nephropathy group and control group A, and the positive expression rate of TLR3 and TLR4 in peripheral blood mononuclear cells were detected by using flow cytometry in IgA nephropathy group.The expression of TLR3 and TLR4 in peripheral blood mononuclear cells of IgA nephropathy group and control group B were observed and compared. Results The expressions of TLR3 and TLR4 in renal tissue of IgA nephropathy group were respectively (68.28±6.37)% and 0.048±0.018, which were significantly higher than TLR3 [(9.69±11.02)%] and TLR4 (0.003±0.001) in the control group A, and the differences were statistically significant (t=50.080, 14.374, all P<0.01). The positive expressions of TLR3 and TLR4 in peripheral blood mononuclear cells of IgA nephropathy group were respectively (17.62±8.33)% and (23.85±11.82)%, while the expressions were (0.31±0.06)% and (3.02±0.09)% respectively in the control group B, and the differences were statistically significant (t=12.109, 11.612, all P<0.05). Conclusion The expressions of TLR3 and TLR4 in renal tissue and peripheral blood mononuclear cells of IgA nephropathy are increased, suggesting that the abnormal activation of TLR3 and TLR4 may be involved in the pathogenesis of IgA nephropathy. Key words: Toll like receptor 3; Toll like receptor 4; IgA nephropathy; Peripheral blood mononuclear cell; Renal tissue

The significance of Toll-like receptor (TLR) 2 and 9 gene polymorphisms in psoriasis.

The significance of Toll-like receptor (TLR) 2 and 9 gene polymorphisms in psoriasis.

Клиническое значение Toll-подобных рецепторов в патогенезе преждевременных родов

Клиническое значение Toll-подобных рецепторов в патогенезе преждевременных родов

Significance of Toll-like Receptor 4 Signaling in Peripheral Blood Monocytes of Pre-eclamptic Patients

Objective: Preeclampsia (PE) is a serious condition affecting pregnant women and placing both the mother and fetus at risk. While little is known about the pathogenesis of PE, there is evidence for involvement from the maternal innate immune system, specifically, signaling arising from monocytes. The present study was to explore the role of Toll-like receptor (TLR) 4 on peripheral blood monocyte in the pathogenesis of PE. Methods: This study included 22 patients with established preeclampsia and 23 healthy pregnant women (HP). All participants gave informed written consent for 4 mL of fresh venous blood to be collected into a tube containing heparin. The expression of TLR4 on monocytes was evaluated by flow cytometry (FCM). Monocytes were stimulated with LPS for 18 h and cytokine secretion (IL-6, IL-12P70, IL-10, and TNF-α) in supernatants was analyzed with Luminex platform (Luminex Corporation, Austin, TX). The expression of TLR4 and cytokine secretion (IL-6, IL-12P70, IL-10, and TNF-α) was compared between women with PE and healthy pregnant women. Results: Compared with controls, the percentage of TLR4+ monocytes was significantly higher in PE patients. Collected monocytes stimulated with lipopolysaccharide (LPS) to induce inflammation had increased cytokine production, and monocytes from PE patients produced more IL-6 and TNF-α, and less IL-10 than cells from healthy participants. PE patients also showed a positive correlation between the percentage of TLR4+ monocytes and serum levels of IL-6 and TNFα. Conclusions: These results suggest that TLR4 signaling may play a role in the pathogenesis of preeclampsia.

Expression Profile and Clinical significance of Toll-like Receptor 9 in Peripheral Blood B Lymphocytes and Kidney Tissues from Patients with IgA Nephropathy

Expression Profile and Clinical significance of Toll-like Receptor 9 in Peripheral Blood B Lymphocytes and Kidney Tissues from Patients with IgA Nephropathy

The expression and significance of toll-like receptor 4 in the ischemia-reperfusion injury of bile duct

Objective To investigate the dynamicexpression process of toll-like receptor 4(TLR4) in rabbits model when the bile duct is in ischemia-reperfusion(I/R)injury, explore the relationship between the I/R injury of bile duct and the activation of TLR4. Methods Creat rabbits model of bile duct I/ R injury.The control group only dissect the Hepatic portal, without ischemia and reperfusion, the experimental group in each group ischemia time was 2 hours and reperfusion time was 0,6,12,18,24 h,at different reperfusion time point draw and observed the injury of bile duct by optical microscopy and electron microscopy, through immunohistochemistry to observe the expression of TLR4 in the bile duct epithelial cell, testing the expression of R-glutamyltranspeptidase(GGT),alkaline phosphatase(AKP), total bilirubin(TBIL)of veinal blood, and statistical analysis. Results At different reperfusion time point, TLR4 was expressed in bile duct epithelial cell of experimental group, the numbers of positive cells in each group is sham operation group:8±2;I/R 0,6,12,18,24 h group was 26±11,49±6,98±14,38±7,18± 5, experimental group compared with the control group, the difference was statistically significant(P< 0. 05).With the extension of reperfusion time,the TBIL, GGT, AKP gradually increased, and gradually decreased after peaked at 12 hours[respectively ALP:(3. 22±0. 82)IU/L; GGT:(96. 17±23. 20)IU/ L; TBIL:(6. 30±1. 03)μmol/L],the change between the experimental group and the control group was significantly,the difference was statistically significant(P<0. 05). Conclusion The activation of TLR4 involved in the progress of I/R injury of rabbits,irreversible damage such as cell swelling and mitochondrial swelling will be happened in the liver cell and bile duct epithelial cell, when within two hours of I/Rinjury, TBIL, GGT, AKP can be an indicator as the detection of bile duct I/R injury. Key words: Liver transplantation; Ischemia-reperfusion injury of bile duct; Toll-like receptor 4

Expression of Toll-like receptor 3 and Toll-like receptor 4 in peripheral blood mononuclear cells from Henoch-Schönlein purpura nephritis in children and its clinical significance

Objective To explore the expressions and clinical significance of Toll-like receptor (TLR) 3 and TLR4 in peripheral blood mononuclear cells in Henoch-Schonlein purpura nephritis (HSPN) children. Methods According to their 24-hour urinary albumin and whether children with HSP had renal damage or not, 105 cases were divided into group A, B and C. Group A were children only with HSP but without renal damage, while group B were children only with HSPN not proteinuria and group C were children with both HSPN and proteinuria.Thirty healthy children were in healthy control group(group N). Flow cytometry (FCM) and real-time PCR detected the mRNA and protein expressions of TLR3 and TLR4 in peripheral blood mononuclear cells. Results 1.The mRNA and protein expressions of TLR4 in peripheral blood mononuclear cells were significantly higher in group A, B, C than those in group N(F=37.33, 24.01, all P 0.05).2.Moreover, there was a positive relationship between protein expression of TLR4 and 24-hour urinary albumin in group C(r=0.69, P 0.05).4.The expression of TLR4 mRNA had a positive correlation with protein expression of TLR4(r=0.61, P<0.01). Conclusions Expressions of TLR4 in peripheral blood mononuclear cells significantly increased and had a positive correlation with urinary protein excretion from HSPN in children.This implied that aberrant activation of TLR4 might be relevant to the development of HSPN. Key words: Henoch-Schonlein purpura; Child; Henoch-Schonlein purpura nephritis; Toll-like receptor

PPAR-γ AND TOLLIP ARE ASSOCIATED WITH TOLL-LIKE RECEPTORS IN COLITIS RATS

To elucidate the significance of Toll-like receptors and their negative regulating factors PPAR-γ and Tollip on the pathogenesis of colitis. Colitis model was induced by TNBS in rat. The expression of TLR2, TLR4, NF-κBp65, PPAR-γ and Tollip was examined by immunohistochemistry (IHC) and reverse-transcription polymerase chain reaction (RT-PCR). RT-PCR revealed a significant increased expression of TLR2, TLR4, and NF-κBp65 in the colitis group compared with the normal group (TLR2: 1.057 ± 0.092, 0.463 ± 0.101, t = 4.125, P = 0.001; TLR4: 0.376 ± 0.029, 0.215 ± 0.049, t = 2.731, P = 0.013; NF-κBp65: 0.746 ± 0.049, 0.206 ± 0.063, t = 6.055, P = 0.000). The expression was positively correlated with the generally damage score and the histological injury score correspondingly (TLR2: r = 0.573, r = 0.559; TLR4: r = 0.754, r = 0.866; NF-κBp65: r = 0.548, r = 0.919). The Tollip mRNA wasn't obviously diversity between the normal and colitis groups by RT-PCR (Tollip: 0.288 ± 0.050, 0.140 ± 0.046, t = 1.993, P = 0.061). While the Tollip protein was mainly assembled in the lamina propriaand higher in the colitis group compared with the normal group by IHC. The expression of PPAR-γ in the colitis group was obviously lower than that in the normal group (PPAR-γ: 0.255 ± 0.065, 0.568 ± 0.072, t = 2.882, P = 0.010). The expression of Tollip and PPAR-γ was negative correlated with the generally damage score and histological injury score correspondingly (Tollip: r = −0.497, r = −0.551; PPAR-γ: r = −0.683, r = −0.853). The disbalance between TLRs and their negative regulating factors PPAR-γ and Tollip was closely associated with the course of colitis.

Expression and significance of Toll-like receptor 3 in human pulmonary adenocarcinoma cells

Objective To investigate the expression and significance of Toll-like receptor 3 (TLR3)in human pulmonary adenocarcinoma cells (A549) and human bronchial epithelial cells (HBEs).Methods The A549 cells and HBEs were cultured in vitro.The expression of TLR3 in both cells was detected by using immunocytochemistry.The expression of TLR3 mRNA and protein in both cells was detected bv using real-time quantitative polymerase chain reaction (Real-time PCR) and Western blotting respectively.Results Immunocytoehemistry staining revealed that TLR3 was mainly expressed and stained brown-yellow in cell membrane and endochylema.The expression of TLR3 mRNA and protein in A549 cells was stronger than that in HBEs.The relative expression values of TLR-3 mRNA in A549 cells and HBE cells were 1.0168 ± 0.02376 and 0.0478 ± 0.01792 respectively.The relative expression values of TLR-3 protein in A549 cells and HBEs were 0.3193 ± 0.01116 and 0.1607 ± 0.00303 respectively (P ＜ 0.01).Conclusion TLR3 might cause the progression of human pulmonary adenocarcinoma. Key words: Pulmonary adenocarcinoma; Toll-like receptor 3; Immunocytochemistry

Specific expression and significance of Toll-like receptor 4 in pancreatic tissue of non-obesediabetic mice

Objective To detect the expression of Toll-like receptor 4 (TLR4) in pancreas of non-obesediabetic (NOD) mice and the change in the pathogenesis in order to explore their clinical significance.Methods Immunofluorescence was used to detect the location of TLR4 in pancreas,reverse transcription-polymerase chain reaction (RT-PCR) and Western blotting were employed to examine its mRNA and protein expression changes in the pathogenesis of type 1 diabetes separately.Results TLR4 was expressed on almost all the surface of β islet cells.With the development of the type 1 diabetes,the relative expression of TLR4 was elevated from ( 1.01 ±0.01 ) to (3.68 ±0.10),P ＜0.01 ; the relative expression of TLR4 mRNA was elevated from ( 1.00 ±0.02) to (4.76 ±0.17),P ＜0.01.Conclusion The expression of TLR4 is significantly increased with the progress of type 1 diabetes,suggesting that TLR4 may participate in the occurrence and development of type 1 diabetes by immune mechanisms. Key words: Type 1 diabetes; Toll-like receptor 4 ; Pancreas

The Significance of Toll-Like Receptors in the Development of Ischemic Damage

A role of immune processes in the development of ischemic lesion is reviewed. Special attention is drawn to key receptors of innate immunity--Toll-like receptors (TLR). Main types of these receptors, their ligands, key mechanisms involved in the TLR signal transduction are characterized. The data of experimental and clinical studies of innate immunity factors in the development of ischemic stroke and myocardial infarction are summarized. The authors discuss the similarity of results, the main causes of which may be the evolutional conservatism of TLR and presence of the common pathological process (artery atherosclerosis) in different vascular beds as a common cause that underlie brain and myocardial ischemia.

Differential expression and its significance of Toll like receptors in human breast cancer cells with different invasive capacities

Objective To study the expression and significances of Toll like receptors (TLRs) in human high invasive breast cancer cells MDA-MB-231 and poor invasive breast cancer cells MCF-7. Methods TLRs mRNA expression levels were detected in breast cancer cell lines MDA-MB-231 and MCF-7 by reverse transcription-polymerase chain reaction (RT-PCR) and real-time PCR. TLRs protein expression levels were detected by flow cytometry (FCM) and immunofluorescence methods. Results Human breast cancer cell lines MDA-MB-231 and MCF-7 expressed TLRs including TLR1-TLR10 at both mRNA and protein levels. The mRNA expression of TLR4, TLR6, TLR8 and TLR9 in MDA-MB-231 cells was obviously higher than that in MCF-7 cells respectively, and the expression in MDA-MB-231 cells was (39.4 ±3. 2),(10. 8 ± 2. 4), (5. 8 ± 2. 6 ) and (3. 2 ± 2. 5) times as much as that in MCF-7 cells respectively ( P ＜0. 01). Protein expression of TLR4, TLR6, TLR7 and TLR5 in MDA-MB-231 cells was significantly higher than that in MCF-7 cells respectively, and the expression in MDA-MB-231 cells was (6.4 ± 1.6),(4. 1 ± 0. 9), (3. 7 ± 0. 8 ) and (2. 8 ± 0.4) times as much as that in MCF-7 cells respectively ( P ＜0. 01). Conclusion TLR1-TLR10 was expressed widely and differentially in human breast cancer cell lines MDA-MB-231 and MCF-7. TLR4 mRNA and protein levels were the highest out of TLR1-TLR10.The differential expressions of TLRs may be related to the invasion capacity of human breast cancer cells.TLR4 may provide basement for breast cancer target gene therapy. Key words: TLRs; Breast carcinoma ; Invasion

EXPRESSION OF TOLL-LIKE RECEPTOR 4, CD14, AND NF-κB IN CHINESE PATIENTS WITH ULCERATIVE COLITIS

This study elucidates the significance of Toll-like receptor 4 (TLR4), CD14, and nuclear factor (NF)-κB on the pathogenesis of ulcerative colitis (UC). Colonic biopsy specimens were collected from active UC and controls. The expression of TLR4, CD14, and NF-κBp 65 was analyzed by immunohistochemistry (IHC) and reverse-transcription polymerase chain reaction (RT-PCR). In UC, disease activity index (DAI) and pathological grade were classified according to the Powell–Tuck grade system and Truelove–Richards system, respectively. Fifty-six UC cases and 56 controls entered the investigation. IHC and RT-PCR revealed a significant increase of TLR4, CD14, and NF-κBp 65 antigen expression in colonic mucosa of UC compared with colonic mucosa of controls (p < .001). In UC, TLR4, CD14, and NF-κBp 65 expression were positively related to DAI (r = .873, p < .001; r = .576, p < .001; r = .747, p < .001 receptively). NF-κBp65 significantly correlated with TLR4 and CD14 (r = .669, p < .001; r = .576, p < .001, receptively). TLR4, CD14, and NF-κBp65 were positively related to pathological classification in UC (p < .01). Thus, TLR4, CD14, and NF-κBp65 were upregulated significantly in UC, to an extent that reflects the degree of inflammation and thereby might contribute to the occurrence and development of UC.

Correlation of toll-like receptor 3 and tumor necrosis factor-alpha with idiopathic fetal growth restriction.

To investigate the expression and the significance of toll-like receptor 3 (TLR-3) in placenta, tumor necrosis factor-alpha(TNF-alpha) in maternal and cord blood of idiopathic fetal growth restriction (IFGR), and their correlation with the pathogenesis of symmetric and asymmetric IFGR. From April 2008 to April 2009, 42 primiparae of singleton pregnancy and their IFGR babies, who delivered at term through cesarean section, in the Third Affiliated Hospital of Zhengzhou University were enrolled. All subjectects were divided into symmetric IFGR group (n = 20) and asymmetric IFGR group (n = 22). Another 42 non-IFGR pairs were randomly selected as the control group. The polink-2 plus polymerized horseradish peroxidase (HRP) immunohistochemical method and the enzyme linked immunosorbent assay (ELISA) were applied to detect TLR-3 and TNF-alpha levels. (1) The expression of TLR-3 protein were observed in all maternal placenta of the three groups. TLR-3 essentially expressed in syncytiotrophoblasts and hofbouer cells in the symmetric IFGR and control group, but expressed mostly in hofbouer cells and less in syncytiotrophoblasts in the asymmetric IFGR group. (2) The expression of TLR-3 in the syncytiotrophoblasts of the symmetric and asymmetric IFGR group was significantly lower than in the control group (111 +/- 14 and 118 +/- 11 vs. 156 +/- 9, P < 0.01). The number of TLR-3 positive in Hofbourer cell in the symmetric IFGR group was lower than the control group (8.9 +/- 2.8 vs 17.5 +/- 2.8, P < 0.01), but the number in the asymmetric IFGR group was higher (23.8 +/- 3.7) compared with the control group (P < 0.01). (3) The TNF-alpha levels in the maternal and cord blood of the symmetric and the asymmetric group were higher than that of the control group [maternal: (90 +/- 10) microg/L and (86 +/- 11) microg/L vs. (73 +/- 9) microg/L; cord blood: (92 +/- 12) microg/L and (96 +/- 8) microg/L vs. (79 +/- 9) microg/L; P < 0.01]. (4) Neither symmetric nor the asymmetric IFGR group showed any correlations between the maternal and cord blood levels of TNF-alpha (P > 0.05). (5) Significant correlation was found between the TNF-alpha level of the cord blood and TLR-3 expression in the placenta in both the symmetric and asymmetric IFGR group (P < 0.05), but no relationship was found between the maternal blood TNF-alpha level and TLR-3 expression in the placenta (P > 0.05). The variantions of TLR-3 expression in placenta and the increased expression of TNF-alpha in cord blood are associated with the genesis IFGR. The reduced expression of TLR-3 may related to symmetric IFGR, while the increased TLR-3 level in hofbouer cells may lead to asymmetric IFGR.

The significance of toll-like receptors in human diseases

Toll-like receptors (TLRs) are a family of transmembrane receptors that have been preserved throughout evolution and which selectively recognize a broad spectrum of microbial components and endogenous molecules released by injured tissue. Identification of these ligands by TLRs triggers signalling pathways which lead to the expression of numerous genes involved in a defensive response. In mammals, the products of these genes initiate inflammation, coordinate the effector functions of innate immunity, instruct and modulate adaptive immunity and initiate tissue repair and regeneration. Different mutations and experimental models which alter TLR function have revealed the significance of these receptors in susceptibility to infection and their involvement in the pathogenesis of a large number of non-infective inflammatory disorders such as cancer, allergy, autoimmunity, inflammatory bowel disease, or atherosclerosis. TLRs are currently viewed as important targets for the development of new vaccines and innovative therapies to prevent and treat human diseases.

The significance of Toll-like receptor 4 (TLR4) expression in patients with chronic hepatitis B

To investigate the importance of Toll-like receptor 4 (TLR4) expression on hepatocytes obtained from Chronic Hepatitis B patients as well as on hepatocellular carcinoma HepG2 and HepG2.2.15 cell lines. Expression of TLR4 in liver tissues was determined by immunohistochemistry in 75 patients with CHB and in10 healthy controls. The protein and mRNA 1eve1s of TLR4 in hepatocellular carcinoma HepG2 and HepG2.2.15 cells were measured by flow cytometry (FCM) and real-time quantitative PCR (RQ-PCR), and endotoxin triggered TNF-alpha secretion in HepG2 and HepG2.2.15 cells was evaluated by ELISA. TLR4 expressed mainly in the cytoplasm and some on cell membrane in hepatocytes. The staining scores of TLR4 expression in the liver tissues of patients with CHB were significantly higher than that of healthy controls. The liver tissues from patients with severe CHB expressed higher level of TLR4 than those from patients with mild CHB. Furthermore, the staining scores of TLR4 expression in the liver tissues of patients with CHB were positively correlated with the grading scores. Our results also showed that the mean fluorescence intensity and TNF-alpha secretion induced by endotoxin as well as the protein and mRNA 1eve1s of TLR4 in HepG2.2.15 cells were all significantly higher than those in HepG2 cells. TLR4 was up-regulated in the hepatocytes in patients with CHB. This indicates a potentially important interaction between TLR4 expression and the pathogenesis of CHB.