Relationship of Toll-Like Receptors 2 and 4 Gene Polymorphisms with Essential Hypertension in Chinese Han Population

Objective: There are numerous studies suggesting that genetic polymor-phisms of inflammation factors Toll-like receptors 2 and 4 (TLR2, TLR4) might play a role in the pathophysiological process of hypertension. In this study, we evaluated the association in a sample of members of the Chinese Han population. Method: We selected four single nucleotide polymor-phisms (SNP) of TLR2 (rs3804099, rs3804100, rs7656411) and TLR4 (rs1927906) genes, and measured the distributions of genotypic and allelic frequencies in 1063 participants, including 391 essential hypertension pa-tients and 672 controls. Result: No significant differences in the genotypic and allelic frequencies of the four SNPs were detected between cases and controls. However, three haplotypes, CCG, TTG and TTT of TLR2, were significantly associated with a decrease in the risk of essential hyperten-sion (OR: 0.512, 95% CI: 0.397 - 0.660, P P = 0.0038;OR: 0.797, 95% CI: 0.667 - 0.952, P = 0.0122, respectively). Inversely, the risk of essential hypertension increased sig-nificantly in patients with the CTG, TCG or TCT haplotypes (OR: 2.924, 95% CI: 2.157 - 3.963, P P P Conclusion: Our study suggested that haplotypes (CCG, TTG, TTT, CTG, TCG and TCT) of TLR2 might have profound effects on the development of essential hypertension in the Chinese Han population.

Expression and Implication of Toll-like Receptors TLR2,TLR4 and TLR9 in Colonic Mucosa of Patients with Ulcerative Colitis

Toll-like receptors （TLRs） family may play important roles in inflammatory bowel dis- ease. This study examined the expression of TLR2, TLR4 and TLR9 in the colonic tissues of patients with ulcerative colitis 0AC） and explored their roles in the pathogenesis of UC. Colonic biQpsies were taken from the colon of 30 patients with mild or moderate UC （at active phase） and 10 healthy con- trois during colonoscopy. TLR2, TLR4 and TLR9 protein expression levels were immunohisto- chemically detected. The mRNA expression levels of TLR2, TLR4 and TLR9 were assessed by re- verse transcription polymerase chain reaction （RT-PCR）. The disease activity index （DAI）, colono- scopic and histologic grades and fecal microbial flora were determined. Histological examination showed that the intestinal mucous membrane of UC patients underwent acute inflammation changes. Immunohistochemistry exhibited that the expression levels of TLR2, TLR4 and TLR9 in colon epi- thelia and inflammatory cells were higher in UC patients than in control group （P〈0.01）. The mRNA expression levels of TLR2, TLR4 and TLR9 were increased in UC patients but were not detected in the normal controls. Expression levels ofTLR2, TLR4 and TLR9 were positively correlated, and bore close correlation with DAI, colonoscopic and histologic grades and fecal microbial flora. An impor- tant mechanism of UC might be that abnormal activation of mucosal immunity by intestinal dysbac- teriosis caused dysregulation of TLRS that mediates innate immunity.

Activation of Toll-like receptors signaling in non-small cell lung cancer cell line induced by tumor-associated macrophages

Background： Inflammation is often linked with the progress and poor outcome of lung cancer. The understanding of the relationship between tumor-associated macrophages （TAMs） and lung cancer cells involves in the underlying mechanism of inflammatory cytokine production. Toll-like receptors （TLRs） are engaged in promoting the production of pro-inflammatory cytokines and play an important role in tumor immunology. Methods： To investigate the mechanisms by which TAMs influence the production of pro-inflammatory cytoldnes in lung cancer cells, we established an in vitro coculture system using TAMs and human non- small cell lung cancer （NSCLC） cell line SPC-A1. Levels of interleukin （IL）-113, IL-6 and IL-8 in SPC-A1 were evaluated by RT-PCR and cytometric bead array assay after being cocultured with TAMs. Expression changes of TLRs and TLRs signaling pathway proteins in SPC-Al were further confirmed by RT-PCR and western blot. The level changes of IL-1β, IL-6 and IL-8 in SPC-Al were also detected after the stimulation of TLRs agonists. Results： We found that the phenotype markers of TAMs were highly expressed after stimulating human monocyte cell line THP-1 by phorbol-12-myristate-β-acetate （PMA）. Higher mRNA and supernate secretion levels of IL-1β, IL-6 and IL-8 were detected in SPC-A1 after being eocultured with TAMs. We also found that TLR1, TLR6 and TLR7 were up-regulated in SPC-A1 in the coculture system with TAMs. Meanwhile, TLRs signaling pathway proteins were also significantly activated. Moreover, pre-treatment with agonist ligands for TLR1, TLR6 and TLR7 could dramatically promote inductions of IL-1β, IL-6 and IL-8. Conclusions： These findings demonstrated that TAMs may enhance IL-1β, IL-6 and IL-8 expressions via TLRs signaling pathway. We conclude that TAMs contribute to maintain the inflammation microenvironment and ultimately promote the development and progression of lung cancer.

The role of Toll-like receptors in retinal ischemic diseases

Toll-like receptors（TLRs） are commonly referred to a series of evolutionary conserved receptors which recognize and respond to various microbes and endogenous ligands.Growing evidence has demonstrated that the expression of TLRs in the retina is regulated during retinal ischemic diseases,including ischemia-reperfusion injury,glaucoma,diabetic retinopathy（DR） and retinopathy of prematurity（ROP）.TLRs can be expressed in multiple cells in the retina,such as glial cells,retinal pigment epithelium（RPE）,as well as photoreceptor cells and endothelium cells.Activation of TLRs in retina could initiate a complex signal transduction cascade,induce the production of inflammatory cytokines and regulate the level of costimulatory molecules,which play prominent roles in the pathogenesis of retinal ischemic diseases.In this review,we summarized current studies about the relationship between TLRs and ischemic retinopathy.A greater understanding of the effect of TLRs on ischemic injuries may contribute to the development of specific TLR targeted therapeutic strategies in these conditions.

Expression of Chicken Toll-Like Receptors and Signal Adaptors in Spleen and Cecum of Young Chickens Infected with Eimeria tenella

Toll-like receptors （TLRs） are a group of highly conserved molecules which initiate the innate immune response to pathogens by recognizing structural motifs of microbes. Understanding the changes in chicken Toll-like receptors （ChTLRs） and signal adaptors expression that occur with Eimeria tenella infection will help to elucidate the molecular basis of immune control of coccidiosis caused by Eimeria. The present study detected the dynamic changes in the expression of ChTLRs and associated signal adaptors in the spleen and cecum ofE. tenella-infected chickens during the early stage of infection. The results showed that the expression peak for ChTLRs, MyD88 and TRIF occurred at 12 h post-infection （hpi）, ChTLR3, ChTLRI 5 and MyD88 mRNA expression in the spleen ofE. tenella infected chickens were significantly higher （P〈0.05） than that of negative control chickens, and there were similar tendencies of these molecules expression in the cecum and spleen of E. tenella-infected chickens. The expression of MyD88 was upregnlated at four time points in the cecum of E. tenella-infected chickens. The results of this study indicate that ChTLR3, ChTLR15 and MyD88 play a role in young chickens infected with E. tenella.

Toll-like receptors and hepatitis C virus infection

Background:Hepatitis C virus(HCV)infection is a worldwide issue.However,the current treatment for hepatitis C has many shortcomings.Toll-like receptors(TLRs)are pattern recognition receptors involved in HCV infection,and an increasing number of studies are focusing on the role of TLRs in the progression of hepatitis C.Data sources:We performed a Pub Med search up to January 2021 with the following keywords:hepatitis C,toll-like receptors,interferons,inflammation,and immune evasion.We also used terms such as single-nucleotide polymorphisms(SNPs),susceptibility,fibrosis,cirrhosis,direct-acting antiviral agents,agonists,and antagonists to supplement the query results.We reviewed relevant publications analyzing the correlation between hepatitis C and TLRs and the role of TLRs in HCV infection.Results:TLRs 1–4 and 6–9 are involved in the process of HCV infection.When the host is exposed to the HCV,TLRs,as important participants in HCV immune evasion,trigger innate immunity to remove the virus and also promote inflammation and liver fibrosis.TLR gene SNPs affect hepatitis C susceptibility,treatment,and prognosis.The contribution of each TLR to HCV is different.Drugs targeting various TLRs are developed and validated,and TLRs can synergize with classic hepatitis C drugs,including interferon and direct-acting antiviral agents,constituting a new direction for the treatment of hepatitis C.Conclusions:TLRs are important receptors in HCV infection.Different TLRs induce different mechanisms of virus clearance and inflammatory response.Although TLR-related antiviral therapy strategies exist,more studies are needed to explore the clinical application of TLR-related drugs.

Toll-Like Receptors as Biomarkers of Gastric Carcinogenesis:Implications for Diagnosis,Prognosis and Treatment

Toll-like receptors (TLR) are essential for Helicobacter pylori (Hp) recognition and subsequent innate and adaptive immunity responses. TLR2 appears to be the receptor responsible for most of the immunologic reaction against Hp infection. However, TLR4, TLR9 and eventually TLR5 may also have a synergic effect with TLR2 against Hp. It has been shown that gastric Hp infection increases TLR expression in the gastric mucosa. Moreover, recent studies have shown that human gastric carcinogenesis is associated not only with increased expression of TLR but also with decreased expression of their inhibitors such as Toll-Interacting Protein (TOLLIP) and peroxisome proliferator-activated receptor (PPAR)-g. Indeed, gastric dysplasia and adenocarcinoma are associated with high expression levels of TLR and low levels of TOLLIP and PPAR-g, suggesting increased activation of these receptors throughout human gastric carcinogenesis. In this article we discuss how these novels findings could be used not only for the diagnosis and prognosis of gastric lesions associated with Hp infection but also for their treatment. Specifically, we discuss the potential use of TLR agonists in addition to antibiotics to improve eradication rates of Hp and of TLR antagonists to slow the progression of gastric preneoplastic lesions. We also discuss the potential value of TLR signalling blockers and quantification of tumoral TLR expression, respectively, in the treatment and prognosis of gastric cancer. In conclusion, TLRs can be an important link between Hp and the sequence of gastric carcinogenesis and they can be used as biomarkers of gastric carcinogenesis. In this article, future lines of investigation related with these novel scientific findings are proposed and discussed.

Controversial role of toll-like receptors in acute pancreatitis

Acute pancreatitis(AP)is a common clinical condition with an incidence of about 300 or more patients per million annually.About 10%-15%of patients will develop severe acute pancreatitis(SAP)and of those, 10%-30%may die due to SAP-associated complications.Despite the improvements done in the diagnosis and management of AP,the mortality rate has not significantly declined during the last decades.Toll-like receptors(TLRs)are pattern-recognition receptors that seem to play a major role in the development of numerous diseases,which make these molecules attractive as potential therapeutic targets.TLRs are involved in the development of the systemic inflammatory response syndrome,a potentially lethal complication in SAP.In the present review,we explore the current knowledge about the role of different TLRs that have been described associated with AP.The main candidate for targeting seems to be TLR4,which recognizes numerous damage-associated molecular patterns related to AP.TLR2 has also been linked with AP,but there are only limited studies that exclusively studied its role in AP.There is also data suggesting that TLR9 may play a role in AP.

Effect of ω-3 Polyunsaturated Fatty Acid on Toll-like Receptors in Patients with Severe Multiple Trauma

This study examined the effects of ω-3 polyunsaturated fatty acid（ω-3PUFA） on the expression of toll-like receptor 2（TLR2）,toll-like receptor 4（TLR4） and some related inflammatory factors in peripheral blood mononuclear cells（PBMCs） of patients with early-stage severe multiple trauma.Thirty-two patients who were admitted to the Department of Traumatic Surgery,Tongji Hospital（Wuhan,China） between May 2010 and November 2010,and diagnosed as having severe multiple trauma with a injury severity score（ISS） no less than 16,were enrolled in the study and divided into two groups at random（n=16 in each）：ω-3PUFA group and control group in which routine parenteral nutrition supplemented with ω-3PUFA or not was administered to the patients in two groups for consecutive 7 days.Peripheral blood from these patients was collected within 2 h of admission（day 0）,and 1,3,5 and 7 days after the nutritional support.PBMCs were isolated and used for detection of the mRNA and protein expression of TLR2 and TLR4 by using real-time PCR and flow cytometry respectively,the levels of NF-κB by quantum dots-based immunofluorescence assay,the levels of TNF-α,IL-2,IL-6 and COX-2 by ELISA,respectively.The results showed that the mRNA and protein expression of TLR2 and TLR4 in PBMCs was significantly lower in ω-3PUFA group than in control group 5 and 7 days after nutrition support（both P0.05）.The levels of TNF-α,IL-2,IL-6 and COX-2 were found to be substantially decreased in PBMCs in ω-3PUFA group as compared with control group at 5th and 7th day（P0.05 for all）.It was concluded that ω-3PUFA can remarkably decrease the expression of TLR2,TLR4 and some related inflammatory factors in NF-κB signaling pathway in PBMCs of patients with severe multiple trauma,which suggests that ω-3PUFA may suppress the excessive inflammatory response meditated by the TLRs/NF-κB signaling pathway.

Role of Toll-like receptors in Helicobacter pylori infection and immunity

The gram-negative bacterium Helicobacter pylori(H. pylori) infects the stomachs of approximately half of the world's population. Although infection induces an immune response that contributes to chronic gastric inflammation, the response is not sufficient to eliminate the bacterium. H. pylori infection causes peptic ulcers, gastric cancer and mucosa-associated lymphoid tissue lymphoma. Disease outcome is linked to the severity of the host inflammatory response. Gastric epithelial cells represent the first line of innate immune defence against H. pylori, and respond to infection by initiating numerous cell signalling cascades, resulting in cytokine induction and the subsequent recruitment of inflamma-tory cells to the gastric mucosa. Pathogen recognition receptors of the toll-like receptor(TLR) family mediate many of these cell signalling events. This review dis-cusses recent findings on the role of various TLRs in the recognition of H. pylori in distinct cell types, describes the TLRs responsible for the recognition of individual H. pylori components and outlines the influence of innate immune activation on the subsequent development of the adaptive immune response. The mechanistic iden-tification of host mediators of H. pylori-induced patho-genesis has the potential to reveal drug targets and opportunities for therapeutic intervention or prevention of H. pylori-associated disease by means of vaccines or immunomodulatory therapy.

Toll-like receptors are potential therapeutic targets in rheumatoid arthritis

Toll-like receptors (TLRs) are found on the membranes of pattern recognition receptors and not only play important roles in activating immune responses but are also involved in the pathogenesis of inflammatory disease, injury and cancer. Furthermore, TLRs are also able to recognize endogenous alarmins released by damaged tissue and necrosis and/or apoptotic cells and are present in numerous autoimmune diseases. Therefore, the release of endogenous TLR ligands plays an important role in initiating and driving inflammatory diseases. Increasing data suggest a role for TLR signaling in rheumatoid arthritis, which is an autoimmune disease. Although their involvement is not comprehensively understood, the TLRs signaling transducers may provide potential therapeutic targets.

Novel role of toll-like receptors in Helicobacter pylori-induced gastric malignancy

Helicobacter pylori(H.pylori)infects the human stomach during infancy and develops into chronic activeinflammation.The majority of H.pylori tend to colonize within the mucous gel layer of the stomach.Thestomach lacks its own immune function,thus innateimmunity as the first line of defense is vital for specificimmunity against H.pylori.We review recent discoveries in the pathophysiologic roles of toll-like receptors(TLRs),mainly TLR2 and TLR4,in H.pylori-induced inflammation.In addition,the TLR pathways activated byH.pylori-induced inflammation have been shown to beclosely associated not only with gastric carcinogenesis,but also with formation of the tumor microenvironmentthrough the production of pro-inflammatory cytokines,chemokines,and reactive oxygen species.Althoughthe correlation between single nucleotide polymorphisms of TLRs and gastric cancer risk remains unclear,a recent study demonstrated that STAT3-driven upregulation of TLR2 might promote gastric tumorigenesis independent of inflammation.Further research onthe regulation of TLRs in H.pylori-associated gastriccarcinogenesis will uncover diagnostic/predictive biomarkers and therapeutic targets for gastric cancer.

Interrelationship between Toll-like receptors and infection after orthotopic liver transplantation

Early microbial recognition by the innate immune system is accomplished by Toll-like receptors(TLRs),with resultant initiation of a pro-inflammatory response against infecting organisms.In spite of presence of an abundance of Toll-like receptors on the surface of the liver,gut bacteria does not elicit an inflammatory reaction in healthy individuals due to tolerance to these TLRs,suggesting that the inflammatory responses seen in the liver are the result of breakdown of this tolerance.While orthotopic liver transplantation is often life saving in many instances,death following this procedure is most commonly due to infection that occurs in up to 80%of transplant recipients,most commonly due to microbial causes in up to 70%of cases and viral infections in 20%,while fungal infections affect only 8%of cases.The probability of acquiring infection following hepatic transplantation is heightened due to affection of the innate immune defense mechanisms of the host following this procedure.Single nucleotide polymorphisms of TLRs have been associated with increased likelihood of either development of post-transplant infection or eradication of infecting organism.However,conflicting reports from other studies reveal that prevalence of this single nucleotide polymorphism is not increased in infected patients.

Divergent expression of bacterial wall sensing toll-like receptors 2 and 4 in colorectal cancer

AIM To characterize the expression of toll-like receptors(TLR) 2 and 4 in colorectal cancer(CRC) and in normal colorectal mucosa.METHODS We analysed tissue samples from a prospective series of 118 unselected surgically treated patients with CRC. Sections from formalin fixed, paraffin embedded specimens were analysed for TLR2 and TLR4 expression by immunohistochemistry. Two independent assessors evaluated separately expression at the normal mucosa, at the invasive front and the bulk of the carcinoma, and in the lymph node metastases when present. Expression levels in different locations were compared and their associations with clinicopathological features including TNM-stage and the grade of the tumour and 5-year follow-up observations were analysed.RESULTS Normal colorectal epithelium showed a gradient of expression of both TLR2 and TLR4 with low levels in the crypt bases and high levels in the surface. In CRC, expression of both TLRs was present in all cases and in the major proportion of tumour cells. Compared to normal epithelium, TLR4 expression was significantly weaker but TLR2 expression stronger in carcinoma cells. Weak TLR4 expression in the invasive front was associated with distant metastases and worse cancerspecific survival at 5 years. In tumours of the proximal colon the cancer-specific survival at 5 years was 36.9% better with strong TLR4 expression as compared with those with weak expression(P = 0.044). In contrast, TLR2 expression levels were not associated with prognosis. Tumour cells in the lymph node metastases showed higher TLR4 expression and lower TLR2 expression than cells in primary tumours.CONCLUSION Tumour cells in CRC show downregulation of TLR4 and upregulation of TLR2. Low expression of TLR4 in the invasive front predicts poor prognosis and metastatic disease.

Effect of Ligands to Toll-Like Receptors (TLR) 3, 7 and 9 on Mice Infected with Mouse Hepatitis Virus A59

Mice infected with mouse hepatitis virus A59 (MHV-A59), an enveloped, positive-strand RNA Co-ronavirus, induce hepatitis, thymus involution, IgG2a-restricted hypergammaglobulinaemia, transaminase release and autoantibodies (autoAb) to liver and kidney fumarylacetoacetate hy-drolase (FAH). Since Toll-like receptors (TLR) play a central role in innate immunity, we explored the effects of TLR3, 7 and 9 stimulation on MHV mouse infection. Thus, the animals were treated with Poly (I:C), Loxoribine and CpG, the respective TLR ligands. MHV-infected mice inoculated with Poly (I:C) had significant lower levels of plasma transaminases and Ig, anti-MHV Ab, and uric acid than MHV-infected animals, whereas autoAb to kidney tissue were observed. Loxoribine only produced a slight decrease of uric acid levels and serum Ig. CpG showed deleterious effects on MHV-infected mice, since survival of animals dramatically dropped to about 10%. AutoAb to murine tissues and uric acid release were not affected, whereas transaminases and anti-MHV Ab were slightly elevated. Besides, CpG administration produced a decrease of the high levels of serum Ig induced by the virus. Therefore, results indicated that TLR3 stimulation appeared to protect the animals against the viral infection, whereas CpG aggravated its signs. Loxoribine, the TLR7 ligand, did not show major effects.

Molecular Assessment of Non-Muscle Invasive and Muscle Invasive Bladder Tumors: Mapping of Putative Urothelial Stem Cells and Toll-Like Receptors (TLR) Signaling

Purpose: The main objectives of this study were to characterize and compare the urothelial stem cells (healthy and cancer cells) and TLRs features in the urinary bladder of men without lesionsand with non-muscle-invasive and muscle invasive urothelial tumors. Materials and Methods: Thirty samples of the urinary bladder of 50 to 80-year-old men, with and without diagnosis of malignant urothelial lesions were used. The 30 samples were divided into 3 groups (n = 10 per group): Normal Group;Non-Muscle Invasive Bladder Cancer Group;Muscle Invasive Bladder Cancer Group. The samples were histopathologically and immunohistochemically analyzed. The study was conducted at teaching Hospital of the University of Campinas (UNICAMP). Results: The CD44 and CD133 immunoreactivities were significantly intense in the muscle-invasive cancer group when compared to the other groups. The ABCG2 biomarker demonstrated intense immunoreactivities in both non-muscle and muscle invasive groups, and absent immunoreactivity in the normal group. All groups showed weak CD117 immunoreactivity. Putative Healthy Stem Cells (CD44/CD133/ CD117+) occurred in all groups. Putative Cancer Stem Cells (CD44/CD133/ABCG2+) only occurred in the non-muscle and muscle invasive cancer groups. TLR2 immunoreactivity was significantly lower in the non-muscle invasive cancer group and absent in the muscle invasive cancer group. TLR4 immunoreactivity was significantly lower in both cancer groups. Conclusions: This study leads us to the conclusion that putative cancer stem cell occurrence was sensitive to the decreased in TLR2 and TLR4 immunoreactivities. Also, TLR2 and TLR4 demonstrated their involvement in the regulation of the different biomarkers for putative healthy and cancer urothelial stem cells, probably acting as negative regulators of urothelial carcinogenesis. Taken together data obtained suggest that use of TLRs agonists could be a promising alternative for the treatment of non-muscle and muscle invasive bladder tumors.

The role of Toll-like receptors in non-infectious lung injury

在病原体识别的像使用费的受体(TLR ) 的角色在最近的年里是快速地先进的。然而，进在非传染的织物损害的 TLR 的功能的调查刚开始了。以前，我们和其它表明了那碎裂的 hyaluronan (哈) 在织物损害期间积累。CD44 被要求在织物损害期间清除 HA，并且损害了清理哈在不停的发炎的结果。另外，碎裂哈在损害地点由煽动性的房间刺激煽动性的基因的表示。最近，我们识别了那哈碎片要求 TLR2 和 TLR4 刺激老鼠巨噬细胞生产煽动性的 chemokines 和 cytokines。在一个非传染的肺损害模型，在 TLR2 和 TLR4 缺乏的老鼠显示出煽动性的房间的损害 transepithelial 迁居，增加的织物损害，提高的肺上皮的房间 apoptosis，和减少的幸存。在高分子的质量的表示上的肺上皮的房间哈对尖锐的肺损害和 apoptosis 的保护的老鼠，部分地通过 NF-kappaB 的 TLR 依赖的基础激活。在 TLR2 和 TLR4 的夸大的损害缺乏的老鼠看起来由于上皮的房间上的损害 HA-TLR 相互作用。这些研究识别那个主机矩阵部件哈并且 TLR 相互作用提供开始煽动性的回答的信号，维持上皮的房间完整，并且支持从尖锐的肺损害的恢复。房间研究(2006 ) 16：693-701。做 i：10.1038/sj .cr.7310085；出版联机 2006 年 8 月 8 日。

Toll-like receptors in inflammatory bowel disease-stepping into uncharted territory

Ulcerative colitis and Crohn's disease are chronic relapsing-remitting inflammatory processes of the intestinal tract. The etiology of these diseases is currently unknown. However, inflammation is hypothesized to result from inappropriate activation of mucosal immunity by luminal antigens in genetically susceptible individuals. Toll-like receptors (TLRs) are a family of transmembrane proteins that act as microbial pattern recognition receptors. They are crucial initiators of innate immune responses. The role of TLRs in the pathogenesis of inflammatory bowel disease (IBD) has not been fully elucidated. In this review, we aim to analyze the available data connecting individual TLRs to intestinal inflammation and IBD.

Role of Toll-like receptors in health and diseases of gastrointestinal tract

人胃肠(官方补给) 道被非病原的共栖的微植物群开拓殖民地于并且经常暴露了到许多病原的有机体。为官方补给的动态平衡的维护，主人必须在病原、非病原的有机体之间区别并且开始有效、适当的有免疫力、煽动性的回答。哺乳动物的像使用费的受体(TLR ) 是模式识别受体(PRR ) 的成员在对微生物引起的病原体的天生的细胞的有免疫力的回答和随后的适应有免疫力的回答的开始起一个中央作用的家庭。最近的研究证明了胃肠的上皮细胞表示描绘到日期的几乎所有 TLR 子类型并且在官方补给的道的 TLR 的表示和激活紧并且并列地被调整。这评论在肠的上皮细胞通过 TLR 的表面表示的下面规定在天生的主人和对共栖的细菌的对官方补给的感染和有免疫力的忍耐的维护的适应有免疫力的回答的开发总结 TLR 的关键双角色的当前的理解。

Toll-like receptors in pathophysiology of liver diseases

Toll-like receptors(TLRs) are pattern recognition receptors that participate in host defense by recognizing pathogen-associated molecular patterns alongside inflammatory processes by recognizing damage associated molecular patterns. Given constant exposure to pathogens from gut, strict control of TLR-associated signaling pathways is essential in the liver, which otherwise may lead to inappropriate production of pro-inflammatory cytokines and interferons and may generate a predisposition to several autoimmune and chronic inflammatory diseases. The liver is considered to be a site of tolerance induction rather than immunity induction, with specificity in hepatic cell functions and distribution of TLR. Recent data emphasize significant contribution of TLR signaling in chronic liver diseases via complex immune responses mediating hepatocyte(i.e., hepatocellular injury and regeneration) or hepatic stellate cell(i.e., fibrosis and cirrhosis) inflammatory or immune pathologies. Herein, we review the available data on TLR signaling, hepatic expression of TLRs and associated ligands, as well as the contribution of TLRs to the pathophysiology of hepatic diseases.