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1.
González-Reyes S Fernández JM González LO Aguirre A Suárez A González JM Escaff S Vizoso FJ 《Cancer immunology, immunotherapy : CII》2011,60(2):217-226
Background
Toll-like receptors (TLRs) have garnered an extraordinary amount of interest in cancer research due to their role in tumor progression. By activating the production of several biological factors, TLRs induce type I interferons and other cytokines, which drive an inflammatory response and activate the adaptive immune system. The aim of this study was to investigate the expression and clinical relevance of TLR3, 4, and 9 in prostate cancer. 相似文献2.
Background
The human endometrium is an important site for contact between the host and pathogens ascending the reproductive tract, and thus plays an important role in female reproductive tract immunity. Previous work in our laboratory has suggested that Toll-like receptors (TLRs) are involved in endometrial epithelial recognition of pathogens and that ligation of endometrial TLRs results in the production of cytokines and chemokines important for both immune and reproductive functions of the endometrium. We have also demonstrated cyclic regulation of TLR3 mRNA and protein expression in human endometrium, suggesting that steroid hormones might play a role in the expression and function of TLR3. In this study, the effects of 17beta-estradiol (E2) and progesterone (P) on TLR3 expression and function in endometrial cell lines were investigated. 相似文献3.
Haiwei Yang Jifu Wei Huiyun Zhang Liyan Lin Wei Zhang Shaoheng He 《BMC cell biology》2009,10(1):37-10
Backgroud
Recently, mast cells have been recognized to express several Toll-like receptors (TLRs) on their membrane surfaces, and granulocyte-macrophage colony-stimulating factor (GM-CSF) was reported to be able to alter expression of TLRs and cytokine production in neutrophils. However, whether GM-CSF modulates the expression of TLR and cytokine production in mast cells is not clear. 相似文献4.
Background
Toll-like receptors (TLRs) as pattern recognition receptors, participate in both innate and adaptive immune responses, and seem to play an important role in the pathogenesis of asthma. This study aimed to identify key TLRs involved in antigen induced pulmonary inflammation (AIPI), a rat model for asthma, and to explore the role of TLRs in the disease development.Methods and Findings
E3 rats were sensitized with ovalbumin (OVA)/alum intraperitoneally and intranasally challenged with OVA to induce AIPI model. TLR1-9 and cytokine mRNA expression in spleen, lung and mediastinal lymph node (mLN) tissues were screened by quantitative real-time polymerase chain reaction. TLR7 expression was found to be significantly down-regulated in spleen while TLR3 and TLR8 expression was up-regulated in mLN of AIPI rats. Furthermore, imiquimod (a ligand of TLR7) and TLR3 specific short-hairpin RNA plasmid for RNA interference were administrated, respectively, in vivo to AIPI rats to observe their effects on the disease by assessing various asthmatic parameters. The numbers of total cells, eosinophils, macrophages and lymphocytes were counted according to differential morphology in bronchoalveolar lavage fluid. Serum IgE and OVA specific IgG1 concentration was detected by enzyme-linked immunosorbent assay. The results showed that both TLR7 ligand treatment and TLR3 RNAi in vivo decreased serum IgE level and interleukin-4 mRNA expression.Conclusion/Significance
TLR3 in mLN and TLR7 in spleen both systemically modulate disease development in AIPI rats via altering serum IgE concentration relevant to Th2 responses. And these findings may provide an important clue for further research in the asthma pathogenesis and suggest a new remedy for asthma treatment. 相似文献5.
6.
Nihon-Yanagi Y Terai K Murano T Matsumoto T Okazumi S 《Cancer immunology, immunotherapy : CII》2012,61(1):71-77
Background
Toll-like receptors (TLRs) play an important role in innate immunity by sensing a variety of pathogens and inducing acquired immunity. To test our hypothesis that dysregulation of innate immune responses acts to trigger carcinogenesis, we studied the expression of TLR2 and 4 in sporadic human colorectal cancer tissue. 相似文献7.
8.
Jiin-Haur Chuang Hui-Ching Chuang Chao-Cheng Huang Chia-Ling Wu Yung-Ying Du Mei-Lang Kung Chih-Hao Chen San-Cher Chen Ming-Hong Tai 《Journal of biomedical science》2011,18(1):65
Background
Toll-like receptor-3 (TLR-3) is a critical component of innate immune system against dsRNA viruses and is expressed in the central nervous system. However, it remains unknown whether TLR3 may serve as a therapeutic target in human neuroblastoma (NB). 相似文献9.
Liesu Meng Wenhua Zhu Congshan Jiang Xiaojing He Weikun Hou Fang Zheng Rikard Holmdahl Shemin Lu 《Arthritis research & therapy》2010,12(3):R103
Introduction
Toll-like receptors (TLRs) are involved in both innate and adaptive immune responses and are likely to play a complex role in the pathogenesis of human rheumatoid arthritis (RA) and experimental arthritis. The objective of this study was to identify the key TLR in pristane-induced arthritis (PIA), a rat model for RA, and to clarify its roles in the initiation and maintenance of arthritis. 相似文献10.
Li Zhang Dan Liu Dan Pu Yanwen Wang Li Li Yanqi He Yalun Li Lei Li Weimin Li 《Biological research》2015,48(1)
Background
Mesenchymal stem cells (MSCs) are considered the best candidate in stem cells therapy due to their multipotent differentiation ability, low expression of co-stimulatory molecules (CD80, CD86, CD34 and HLA-II) and immunosuppression effects on in vivo immune responses. MSCs were now widely used in clinical trials but received no encourage results. The major problem was the fate of engrafted MSCs in vivo could not be defined. Some studies indicated that MSCs could induce immune response and result in the damage and rejection of MSCs. As toll like receptors (TLRs) are important in inducing of immune responses, in this study we study the role of TLR7 in mediating the immune status of MSCs isolated from umbilical cord.Results
Our results indicated that TLR7 agonist Imiquimod could increase the proliferation of PBMC isolated from healthy human volunteers and release of lactate dehydrogenase (LDH) in supernatant from PBMC-UCMSCs co-culture system. Flow cytometry and quantitative PCR also confirmed the regulated expression of surface co-stimulatory molecules and pro-inflammatory genes (IL-6, IL-8, IL-12, TGF-β and TNF-α). And the down-regulation expression of stem cell markers also confirmed the loss of stemness of UCMSCs. We also found that the osteo-differentiation ability of UCMSCs was enhanced in the presence of Imiquimod.Conclusion
To our knowledge, this is the first report that activation of TLR7 pathway increases the immunogenicity of UCMSCs. Extensive researches have now been conducted to study whether the change of immune status will be help in tumor rejection based on the tumor-tropism of MSCs. 相似文献11.
Egbert KO Kruithof Nathalie Satta Jia Wei Liu Sylvie Dunoyer-Geindre Richard J Fish 《BMC evolutionary biology》2007,7(1):148
Background
Toll-like receptors (TLR) recognize pathogen-associated molecular patterns and are important mediators of the innate immune system. TLR1 and TLR6 are paralogs and located in tandem on the same chromosome in mammals. They form heterodimers with TLR2 and bind lipopeptide components of gram-positive and gram-negative bacterial cell walls. To identify conserved stretches in TLR1 and TLR6, that may be important for their function, we compared their protein sequences in nine mammalian species(Homo sapiens, Pan troglodytes, Macaca mulatta, Mus musculus, Rattus norvegicus; Erinaceus europaeus, Bos Taurus, Sus scrofa and Canis familiaris). 相似文献12.
Darren Davies Kieran G Meade Shan Herath P David Eckersall Deyarina Gonzalez John O White R Steven Conlan Cliona O'Farrelly I Martin Sheldon 《Reproductive biology and endocrinology : RB&E》2008,6(1):53
Background
The endometrium is commonly infected with bacteria leading to severe disease of the uterus in cattle and humans. The endometrial epithelium is the first line of defence for this mucosal surface against bacteria and Toll-like receptors (TLRs) are a critical component of the innate immune system for detection of pathogen associated molecular patterns (PAMPs). Antimicrobial peptides, acute phase proteins and Mucin-1 (MUC-1) also provide non-specific defences against microbes on mucosal surfaces. The present study examined the expression of innate immune defences in the bovine endometrium and tested the hypothesis that endometrial epithelial cells express functional receptors of the TLR family and the non-specific effector molecules for defence against bacteria. 相似文献13.
Saba Alzabin Philip Kong Mino Medghalchi Andrew Palfreeman Richard Williams Sandra Sacre 《Arthritis research & therapy》2012,14(3):R142
Introduction
Endosomal toll-like receptors (TLRs) have recently emerged as potential contributors to the inflammation observed in human and rodent models of rheumatoid arthritis (RA). This study aims to evaluate the role of endosomal TLRs and in particular TLR7 in the murine collagen induced arthritis (CIA) model.Methods
CIA was induced by injection of collagen in complete Freund''s adjuvant. To investigate the effect of endosomal TLRs in the CIA model, mianserin was administered daily from the day of disease onset. The specific role of TLR7 was examined by inducing CIA in TLR7-deficient mice. Disease progression was assessed by measuring clinical score, paw swelling, serum anti-collagen antibodies histological parameters, cytokine production and the percentage of T regulatory (Treg) cells.Results
Therapeutic administration of mianserin to arthritic animals demonstrated a highly protective effect on paw swelling and joint destruction. TLR7-/- mice developed a mild arthritis, where the clinical score and paw swelling were significantly compromised in comparison to the control group. The amelioration of arthritis by mianserin and TLR7 deficiency both corresponded with a reduction in IL-17 responses, histological and clinical scores, and paw swelling.Conclusions
These data highlight the potential role for endosomal TLRs in the maintenance of inflammation in RA and support the concept of a role for TLR7 in experimental arthritis models. This study also illustrates the potential benefit that may be afforded by therapeutically inhibiting the endosomal TLRs in RA. 相似文献14.
Zhu W Meng L Jiang C He X Hou W Xu P Du H Holmdahl R Lu S 《Arthritis research & therapy》2011,13(3):R103-15
Introduction
Toll-like receptors (TLRs) are likely to play crucial roles in the pathogenesis of rheumatoid arthritis (RA). The aim of this study was to determine the key TLRs in synovium and explore their roles in the activation of fibroblast-like synoviocytes (FLSs) mediated by T cells in arthritis. 相似文献15.
《Cytokine》2015,74(2):225-235
We previously isolated mesenchymal stromal cells from human tonsils (T-MSCs) and showed the potential of these cells to differentiate into the mesodermal lineage and acquire a follicular dendritic cell (FDC) phenotype under cytokine stimulation. Because these T-MSCs were originally isolated from inflamed tonsillar tissues, we were curious about their activation status in response to innate immune stimuli, such as Toll-like receptors (TLRs). Therefore, we analyzed the expression profile of TLRs in T-MSCs and stimulated the T-MSCs with TLR agonists. TLR3 stimuli induced C–C chemokine receptor type 6 expression in T-MSCs after 24 h. Furthermore, results from cytokine arrays showed increases in epithelial neutrophil-activating peptide-78/C-X-C motif chemokine (CXCL) 5, granulocyte chemotactic protein-2/CXCL6, growth-related oncogene-α/CXCL1, interleukin-8/CXCL8, and interferon gamma-induced protein-10/CXCL10. CD54 expression was also increased after TLR3 stimulation. However, co-culturing T-MSCs with human B cells did not induce B-cell proliferation. This suggests that TLR3 stimulates the differentiation of T-MSCs into FDC-like cells and induces chemokine secretion, possibly by recruiting C–X–C chemokine receptor 2-expressing immune cells. In addition, T-MSCs also appeared to exert immunomodulatory effects by inhibiting B-cell proliferation, possibly by down-regulating CD18. 相似文献
16.
Biased distribution of single nucleotide polymorphisms (SNPs) in porcine Toll-like receptor 1 (TLR1), TLR2, TLR4, TLR5, and TLR6 genes 总被引:1,自引:0,他引:1
Shinkai H Tanaka M Morozumi T Eguchi-Ogawa T Okumura N Muneta Y Awata T Uenishi H 《Immunogenetics》2006,58(4):324-330
Toll-like receptors (TLRs) recognize various microbial components and induce immune responses. Polymorphisms in TLRs may influence their recognition of pathogen-derived molecules; swine TLRs are predicted to be associated with responses to infectious diseases such as pneumonia. In this study, we searched for single nucleotide polymorphisms (SNPs) in the coding sequences of porcine TLR1, TLR2, TLR4, TLR5, and TLR6 genes in 96 pigs from 11 breeds and elucidated 21, 11, 7, 13, and 11 SNPs, respectively, which caused amino acid substitutions in the respective TLRs. Distribution of these nonsynonymous SNPs was biased; many were located in the leucine-rich repeats, particularly in TLR1. These data demonstrated that the heterogeneity of TLR genes was preserved in various porcine breeds despite intensive breeding that was carried out for livestock improvement. It suggests that the heterogeneity in TLR genes is advantageous in increasing the possibility of survival in porcine populations.Electronic SupplementaryMaterial Supplementary material is available for this article at 相似文献
17.
Carsten J Kirschning Stefan Dreher Björn Maaß Sylvia Fichte Jutta Schade Mario Köster Andreas Noack Werner Lindenmaier Hermann Wagner Thomas Böldicke 《BMC biotechnology》2010,10(1):31
Background
Toll-like receptor (TLR) 2 is a component of the innate immune system and senses specific pathogen associated molecular patterns (PAMPs) of both microbial and viral origin. Cell activation via TLR2 and other pattern recognition receptors (PRRs) contributes to sepsis pathology and chronic inflammation both relying on overamplification of an immune response. Intracellular antibodies expressed and retained inside the endoplasmatic reticulum (ER-intrabodies) are applied to block translocation of secreted and cell surface molecules from the ER to the cell surface resulting in functional inhibition of the target protein. Here we describe generation and application of a functional anti-TLR2 ER intrabody (αT2ib) which was generated from an antagonistic monoclonal antibody (mAb) towards human and murine TLR2 (T2.5) to inhibit the function of TLR2. αT2ib is a scFv fragment comprising the variable domain of the heavy chain and the variable domain of the light chain of mAb T2.5 linked together by a synthetic (Gly4Ser)3 amino acid sequence. 相似文献18.
19.
《Phytomedicine》2014,21(6):815-823
TLRs are a family of receptors that play a critical role in the pathogenesis of diabetic nephropathy. TGP have been shown to have anti-inflammatory and immuno-regulatory activities. However, the relation between TGP and TLRs on diabetic nephropathy remains unknown. In this study, we examined effects of TGP on immune regulatory TLR2 and 4 in the kidney from streptozotocin-induced diabetic rats. TGP decreased the levels of 24 h urinary albumin excretion rate significantly in diabetic rats. Western blot analysis showed that TGP significantly inhibited the expression of TLR2 and 4, MyD88, p-IRAK1, NF-κB p65, p-IRF3, TNF-α and IL-1β. Quantitative real-time PCR analysis showed that the significantly increased levels of TLR2 and 4, and MyD88mRNA in the kidneys of diabetic rats were significantly suppressed by TGP treatment. Macrophages infiltration were also markedly increased in the kidneys of the diabetic rats, but were significantly inhibited by TGP in a dose-dependent manner. These results suggest that TGP has protective effects on several pharmacological targets in the progress of diabetic nephropathy by selectively blocking TLRs activation in vivo. 相似文献
20.
Mohammad Reza Khakzad Ahmad Saffari Niloofar Mohamadpour Mojtaba Sankian Abdolreza Varasteh Farhad Salari Mojtaba Meshkat 《Reports of Biochemistry & Molecular Biology》2014,3(1):29-37