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1.
Article in Chinese | WPRIM | ID: wpr-828875

ABSTRACT

OBJECTIVE@#To investigate the effects of over-expression of miR-144 on invasion of SMMC-7721 cells and Toll-like receptor (TLR)/myeloid differentiation factor 88 (MyD88) pathway in hepatocellular carcinoma cells.@*METHODS@#The expressions of miR-144 was examined in normal human hepatocyte line HL-7702 and hepatocarcinoma cell line SMMC-7721 using realtime quantitative PCR (qRT-PCR). SMMC-7721 cells were divided into blank group, miR-144 NC group and miR-144 mimics group, and the expressions of miR-144 in each group were detected with qRT-PCR. Cell count kit-8 (CCK8) was used to assess the survival of SMMC-7721 cells, and the cell invasion was evaluated using Transwell assay. The expressions of matrix metalloproteinase-2 (MMP-2), matrix metalloproteinase-9 (MMP-9) and TLR/MyD88 pathway-related proteins in the cells were detected with Western blotting; the effect of 40 μ mol/L MyD88 inhibitor on TLR/MyD88 pathway-related proteins was examined in SMMC-7721 cells.@*RESULTS@#Compared with normal human hepatocytes, SMMC-7721 cells expressed a significantly lower level of miR-144 ( < 0.05). CCK-8 assay showed that test showed that miR-144 over-expression significantly decreased the cell survival rate ( < 0.05), lowered the number of invasive cells, and decreased the expression of MMP-2 and MMP-9 in SMMC-7721 cells ( < 0.05). The expressions of Toll-like receptor 4 (TLR4), MyD88, phosphorylated nuclear factor-kappa B (pNF-κB) and NF-κB protein decreased significantly in miR-144 mimics group and TJ-M2010-2 group ( < 0.05) and were comparable between the two groups ( > 0.05).@*CONCLUSIONS@#Overexpression of miR-144 decreases SMMC-7721 cell survival and invasion by inhibiting TLR/MyD88 pathway.


Subject(s)
Cell Line, Tumor , Humans , Liver Neoplasms , Matrix Metalloproteinase 2 , MicroRNAs , Myeloid Differentiation Factor 88 , NF-kappa B , Signal Transduction , Toll-Like Receptors
2.
Article in Chinese | WPRIM | ID: wpr-826351

ABSTRACT

Platelets are non-nuclear blood cells that are widely involved in physiological and pathological processes.Their main role is to participate in hemostasis and thrombosis.Toll-like receptors(TLRs)are innate immune receptors.Platelets express multiple TLRs and can promote thrombosis by recognizing ligand-induced platelet activation and aggregation.This article reviews the relationship between platelets/TLR and thrombosis and the roles of TLRs in the development of thrombotic diseases.


Subject(s)
Blood Platelets , Hemostasis , Humans , Platelet Activation , Thrombosis , Toll-Like Receptors
3.
Article in Chinese | WPRIM | ID: wpr-878681

ABSTRACT

Ionizing radiation causes the massive apoptosis of human tissue cells,leading to dysfunction of the gastrointestinal tract and hematopoietic system.Thus,high-efficiency,low-toxicity radiation protection drugs are urgently needed.Toll-like receptor agonists have been developed based on the anti-apoptotic mechanism of tumor cells in recent years,which exert their radioprotective effects by activating downstream pathways,mainly nuclear factor-κB.Here we elucidate several agonists of Toll-like receptors involved in radiation protection,with an attempt to inform the research and development of new radiation protection agents.


Subject(s)
Apoptosis , Humans , NF-kappa B , Radiation Protection , Radiation, Ionizing , Radiation-Protective Agents/pharmacology , Toll-Like Receptors/agonists
4.
Korean Circulation Journal ; : 443-457, 2020.
Article in English | WPRIM | ID: wpr-816671

ABSTRACT

BACKGROUND AND OBJECTIVES: We sought to investigate an anti-atherosclerotic and anti-inflammatory effect of sodium-glucose cotransporter-2 (SGLT-2) inhibitors in normoglycemic atherosclerotic rabbit model.METHODS: Male New Zealand white rabbits (n=26) were fed with a 1% high-cholesterol diet for 7 weeks followed by normal diet for 2 weeks. After balloon catheter injury, the rabbits were administered with the Dapagliflozin (1mg/kg/day) or control-medium for 8 weeks (n=13 for each group). All lesions were assessed with angiography, optical coherence tomography (OCT), and histological assessment.RESULTS: Atheroma burden (38.51±3.16% vs. 21.91±1.22%, p<0.01) and lipid accumulation (18.90±3.63% vs. 10.20±2.03%, p=0.047) was significantly decreased by SGLT-2 inhibitor treatment. The SGLT-2 inhibitor group showed lower macrophage infiltration (20.23±1.89% vs. 12.72±1.95%, p=0.01) as well as tumor necrosis factor (TNF)-α expression (31.17±4.40% vs. 19.47±2.10%, p=0.025). Relative area of inducible nitric oxide synthase+ macrophages was tended to be lower in the SGLT-2 inhibitor-treated group (1.00±0.16% vs. 0.71±0.10%, p=0.13), while relative proportion of Arg1⁺ macrophage was markedly increased (1.00±0.27% vs. 2.43±0.64%, p=0.04). As a result, progression of atherosclerosis was markedly attenuated in SGLT-2 inhibitor treated group (OCT area stenosis, 32.13±1.20% vs. 22.77±0.88%, p<0.01). Mechanistically, SGLT-2 treatment mitigated the inflammatory responses in macrophage. Especially, Toll-like receptor 4/nuclear factor-kappa B signaling pathway, and their downstream effectors such as interleukin-6 and TNF-α were markedly suppressed by SGLT-2 inhibitor treatment.CONCLUSIONS: These results together suggest that SGLT-2 inhibitor exerts an anti-atherosclerotic effect through favorable modulation of inflammatory response as well as macrophage characteristics in non-diabetic situation.


Subject(s)
Angiography , Atherosclerosis , Catheters , Constriction, Pathologic , Diet , Humans , Interleukin-6 , Macrophages , Male , Nitric Oxide , Plaque, Atherosclerotic , Rabbits , Toll-Like Receptors , Tomography, Optical Coherence , Tumor Necrosis Factor-alpha
5.
Einstein (Säo Paulo) ; 18: eAO5294, 2020. tab, graf
Article in English | LILACS | ID: biblio-1090061

ABSTRACT

ABSTRACT Objective To analyze and compare the expression of Toll-like receptors by regulatory T cells present in the peritoneal fluid of patients with and without endometriosis. Methods Regulatory T cells were isolated from peritoneal fluid of women with and without endometriosis, collected during surgery, and mRNA was extracted for analysis of Toll-like receptors expression by reverse-transcriptase polymerase chain reaction. Results Patients with endometriosis presented regulatory T cells expressing a larger number and variety of Toll-like receptors when compared to regulatory T cells from patients in the Control Group. Toll-like receptor-1 and Toll-like receptor-2 in regulatory T cells were expressed in both groups. All other expressed Toll-like receptors types were only found in regulatory T cells from the Endometriosis Group. Conclusion Patients with endometriosis had peritoneal regulatory T cells expressing various Toll-like receptors types.


RESUMO Objetivo Analisar e comparar a expressão de receptores do tipo Toll por células T reguladoras presentes no líquido peritoneal de pacientes com endometriose. Métodos Células T reguladoras foram isoladas do líquido peritoneal de mulheres com e sem endometriose, coletadas durante a cirurgia, e o RNAm foi extraído para análise da expressão de receptores do tipo Toll por reação em cadeia da polimerase com transcriptase reversa. Resultados Pacientes com endometriose apresentaram células T reguladoras expressando maior número e variedade de Toll por células quando comparadas com T reguladoras de pacientes do Grupo Controle. Receptores do tipo Toll-1 e receptores do tipo Toll-2 foram expressos em ambos os grupos. Todos os outros tipos de receptores Toll foram encontrados expressos apenas em células T reguladoras do grupo com endometriose. Conclusão Pacientes com endometriose apresentaram células T reguladoras peritoneais expressando vários tipos de receptores tipo Toll.


Subject(s)
Humans , Female , Adolescent , Adult , Young Adult , Ascitic Fluid/pathology , T-Lymphocytes, Regulatory/chemistry , Endometriosis/pathology , Endometrium/pathology , Toll-Like Receptors/analysis , Reference Values , Ascitic Fluid/immunology , Body Mass Index , Case-Control Studies , T-Lymphocytes, Regulatory/immunology , Statistics, Nonparametric , Reverse Transcriptase Polymerase Chain Reaction , Endometriosis/immunology , Endometrium/immunology , Visual Analog Scale
6.
Article in English | WPRIM | ID: wpr-719411

ABSTRACT

Mesenchymal stem cells are classified as multipotent stem cells, due to their capability to transdifferentiate into various lineages that develop from mesoderm. Their popular appeal as cell-based therapy was initially based on the idea of their ability to restore tissue because of their differentiation potential in vitro; however, the lack of evidence of their differentiation to target cells in vivo led researchers to focus on their secreted trophic factors and their role as potential powerhouses on regulation of factors under different immunological environments and recover homeostasis. To date there are more than 800 clinical trials on humans related to MSCs as therapy, not to mention that in animals is actively being applied as therapeutic resource, though it has not been officially approved as one. But just as how results from clinical trials are important, so is to reveal the biological mechanisms involved on how these cells exert their healing properties to further enhance the application of MSCs on potential patients. In this review, we describe characteristics of MSCs, evaluate their benefits as tissue regenerative therapy and combination therapy, as well as their immunological properties, activation of MSCs that dictate their secreted factors, interactions with other immune cells, such as T cells and possible mechanisms and pathways involved in these interactions.


Subject(s)
Animals , Dinoprostone , Homeostasis , Humans , Immunomodulation , In Vitro Techniques , Mesenchymal Stem Cells , Mesoderm , Multipotent Stem Cells , Regeneration , Regenerative Medicine , T-Lymphocytes , Toll-Like Receptors
7.
Article in Korean | WPRIM | ID: wpr-759729

ABSTRACT

Imiquimod, a toll-like receptor agonist, is a topical immunomodulator that induces the production of several cytokines including interferon-alpha, which shows antifibrotic properties. We hypothesized that the antifibrotic effect of imiquimod would soften fibrotic skin lesions. Therefore, we applied topical imiquimod with topical tacrolimus or systemic acitretin in patients with refractory lesions of myxedema, angiolymphoid hyperplasia, and generalized discoid lupus erythematosus and confirmed improvement in fibrotic lesions in these patients. Thus, we conclude that use of imiquimod improves fibrotic skin lesions. This report describes our experience with the treatment of this condition along with a review of the related literature.


Subject(s)
Acitretin , Angiolymphoid Hyperplasia with Eosinophilia , Cytokines , Fibrosis , Humans , Hyperplasia , Interferon-alpha , Lupus Erythematosus, Discoid , Myxedema , Skin , Tacrolimus , Toll-Like Receptors
8.
Immune Network ; : e28-2019.
Article in English | WPRIM | ID: wpr-764018

ABSTRACT

IL-18 is a crucial pro-inflammatory cytokine that mediates chronic intestinal inflammation. Metformin, an anti-diabetic drug, was reported to have ameliorative effects on inflammatory bowel disease. Recently, the mechanism of action of metformin was explained as a modulation of gut microbiota. In this study, fecal microbiota transplantation (FMT) using fecal material from metformin-treated mice was found to upregulate the expression of GLP-1 and pattern-recognition receptors TLR1 and TLR4 for the improvement in hyperglycemia caused by a high-fat diet. Further, FMT downregulated the expression of the inflammatory cytokine IL-18. Within the genera Akkermansia, Bacteroides, and Butyricimonas, which were promoted by metformin therapy, Butyricimonas was found to be consistently abundant following FMT. Our findings suggest that modulation of gut microbiota is a key factor for the anti-inflammatory effects of metformin which is used for the treatment of hyperglycemia.


Subject(s)
Animals , Bacteroides , Diet, High-Fat , Down-Regulation , Fecal Microbiota Transplantation , Gastrointestinal Microbiome , Glucagon-Like Peptide 1 , Hyperglycemia , Inflammation , Inflammatory Bowel Diseases , Interleukin-18 , Metformin , Mice , Toll-Like Receptors
9.
Experimental Neurobiology ; : 547-553, 2019.
Article in English | WPRIM | ID: wpr-763791

ABSTRACT

Synucleinopathies are neurodegenerative disorders characterized by the progressive accumulation of α-synuclein (α-syn) in neurons and glia and include Parkinson's disease (PD) and dementia with Lewy bodies (DLB). In this review, we consolidate our key findings and recent studies concerning the role of Toll-like receptor 2 (TLR2), a pattern recognition innate immune receptor, in the pathogenesis of synucleinopathies. First, we address the pathological interaction of α-syn with microglial TLR2 and its neurotoxic inflammatory effects. Then, we show that neuronal TLR2 activation not only induces abnormal α-syn accumulation by impairing autophagy, but also modulates α-syn transmission. Finally, we demonstrate that administration of a TLR2 functional inhibitor improves the neuropathology and behavioral deficits of a synucleinopathy mouse model. Altogether, we present TLR2 modulation as a promising immunotherapy for synucleinopathies.


Subject(s)
Animals , Autophagy , Dementia , Immunotherapy , Lewy Bodies , Mice , Neurodegenerative Diseases , Neuroglia , Neurons , Neuropathology , Parkinson Disease , Toll-Like Receptor 2 , Toll-Like Receptors
10.
Article in English | WPRIM | ID: wpr-773973

ABSTRACT

OBJECTIVES@#To investigate the protective effects and potential mechanisms of Shenhua Tablet (, SHT) on the toll-like receptors (TLRs)-mediated signaling pathways in a rat model of kidney ischemia-reperfusion injury (IRI).@*METHODS@#Sixty male Wistar rats were randomly divided into 5 groups: sham surgery, model control, astragaloside (150 mg•kg•d), low- and high-dose SHT (1.5 and 3.0 g•kg•d, repectively) groups. One week after drug treatment, rats underwent surgery to establish the IRI models. At 24 h and 72 h after the modeling, serum creatinine (Scr) and blood urea nitrogen (BUN) were analyzed; pathological damage were scored after periodic acid-Schiffstaining. TLR2, TLR4 and myeloid differentiation factor 88 (MyD88) protein and mRNA expressions were detected by inmmunohistochemistry, Western blot and qPCR. Tumor necrosis factor α (TNF-α) and interleukin-6 (IL-6) protein expressions were detected by enzyme linked immunosorbent assay.@*RESULTS@#Compared with the sham group, the model group exhibited severe change in renal function (Scr: 189.42±21.50, P<0.05), pathological damage (damage score: 4.50±0.55, P<0.05), and the expression levels of TLR2, TLR4, MyD88, TNF-α, IL-6 were significantly higher than other groups. Meanwhile, the levels of TLRs in model group showed upward tendency from 24 to 72 h, unparalleled with pathological and functional changes. The aforementioned parameters were alleviated to a certain extent, and, in addition to TLRs, presented the obvious downward trending from the 24 to 72 h after the intervention in the SHT and astragaloside groups relative to the model (P<0.05); in particular, the most significant mitigation of these changes was observed in the SHT-H group (P<0.05).@*CONCLUSION@#TLRs may be an important spot to treat and research in acute kidney injury. SHT could effectively mitigate renal injuries and promote recovery of IRI injuries through suppression of degeneration induced by up-regulation of TLR2 and TLR4 expression levels in the MyD88-dependent signaling pathway and exhibit some dose dependence.


Subject(s)
Animals , Disease Models, Animal , Drugs, Chinese Herbal , Pharmacology , Kidney , Male , Myeloid Differentiation Factor 88 , Genetics , Rats , Rats, Wistar , Reperfusion Injury , Signal Transduction , Tablets , Toll-Like Receptors , Genetics
11.
Article in English | WPRIM | ID: wpr-786203

ABSTRACT

Acute kidney injury (AKI) due to renal ischemia reperfusion (IR) is a major clinical problem without effective therapy and is a significant and frequent cause of morbidity and mortality during the perioperative period. Although the pathophysiology of ischemic AKI is not completely understood, several important mechanisms of renal IR-induced AKI have been studied. Renal ischemia and subsequent reperfusion injury initiates signaling cascades mediating renal cell necrosis, apoptosis, and inflammation, leading to AKI. Better understanding of the molecular and cellular pathophysiological mechanisms underlying ischemic AKI will provide more targeted approach to prevent and treat renal IR injury. In this review, we summarize important mechanisms of ischemic AKI, including renal cell death pathways and the contribution of endothelial cells, epithelial cells, and leukocytes to the inflammatory response during ischemic AKI. Additionally, we provide some updated potential therapeutic targets for the prevention or treatment of ischemic AKI, including Toll-like receptors, adenosine receptors, and peptidylarginine deiminase 4. Finally, we propose mechanisms of ischemic AKI-induced liver, intestine, and kidney dysfunction and systemic inflammation mainly mediated by Paneth cell degranulation as a potential explanation for the high mortality observed with AKI.


Subject(s)
Acute Kidney Injury , Apoptosis , Cell Death , Cell Degranulation , Endothelial Cells , Epithelial Cells , Inflammation , Intestines , Ischemia , Kidney , Leukocytes , Liver , Mortality , Necrosis , Negotiating , Perioperative Period , Receptors, Purinergic P1 , Reperfusion , Reperfusion Injury , Toll-Like Receptors
12.
Immune Network ; : 38-2019.
Article in English | WPRIM | ID: wpr-785823

ABSTRACT

Campylobacter is a worldwide foodborne pathogen, associated with human gastroenteritis. The efficient translocation of Campylobacter and its ability to secrete toxins into host cells are the 2 key features of Campylobacter pathophysiology which trigger inflammation in intestinal cells and contribute to the development of gastrointestinal symptoms, particularly diarrhoea, in humans. The purpose of conducting this literature review is to summarise the current understanding of: i) the human immune responses involved in the elimination of Campylobacter infection and ii) the resistance potential in Campylobacter against these immune responses. This review has highlighted that the intestinal epithelial cells are the preliminary cells which sense Campylobacter cells by means of their cell-surface and cytosolic receptors, activate various receptors-dependent signalling pathways, and recruit the innate immune cells to the site of inflammation. The innate immune system, adaptive immune system, and networking between these systems play a crucial role in bacterial clearance. Different cellular constituents of Campylobacter, mainly cell membrane lipooligosaccharides, capsule, and toxins, provide protection to Campylobacter against the human immune system mediated killing. This review has also identified gaps in knowledge, which are related to the activation of following during Campylobacter infection: i) cathelicidins, bactericidal permeability-increasing proteins, chemokines, and inflammasomes in intestinal epithelial cells; ii) siglec-7 receptors in dendritic cell; iii) acute phase proteins in serum; and iv) T-cell subsets in lymphoid nodules. This review evaluates the existing literature to improve the understanding of human immunity against Campylobacter infection and identify some of the knowledge gaps for future research.


Subject(s)
Acute-Phase Proteins , Antigen-Presenting Cells , Campylobacter Infections , Campylobacter , Cathelicidins , Cell Membrane , Chemokines , Cytosol , Dendritic Cells , Epithelial Cells , Gastroenteritis , Guillain-Barre Syndrome , Homicide , Humans , Immune System , Inflammasomes , Inflammation , T-Lymphocyte Subsets , Toll-Like Receptors
13.
Article in English | WPRIM | ID: wpr-776894

ABSTRACT

Houttuynia cordata polysaccharide (HCP) is extracted from Houttuynia cordata, a key traditional Chinese medicine. The study was to investigate the effects of HCP on intestinal barrier and microbiota in H1N1 virus infected mice. Mice were infected with H1N1 virus and orally administrated HCP at a dosage of 40 mg(kg(d. H1N1 infection caused pulmonary and intestinal injury and gut microbiota imbalance. HCP significantly suppressed the expression of hypoxia inducible factor-1α and decreased mucosubstances in goblet cells, but restored the level of zonula occludens-1 in intestine. HCP also reversed the composition change of intestinal microbiota caused by H1N1 infection, with significantly reduced relative abundances of Vibrio and Bacillus, the pathogenic bacterial genera. Furthermore, HCP rebalanced the gut microbiota and restored the intestinal homeostasis to some degree. The inhibition of inflammation was associated with the reduced level of Toll-like receptors and interleukin-1β in intestine, as well as the increased production of interleukin-10. Oral administration of HCP alleviated lung injury and intestinal dysfunction caused by H1N1 infection. HCP may gain systemic treatment by local acting on intestine and microbiota. This study proved the high-value application of HCP.


Subject(s)
Animals , Cytokines , Metabolism , Drugs, Chinese Herbal , Chemistry , Pharmacology , Therapeutic Uses , Gastrointestinal Microbiome , Houttuynia , Chemistry , Hypoxia-Inducible Factor 1, alpha Subunit , Metabolism , Inflammation , Drug Therapy , Pathology , Influenza A Virus, H1N1 Subtype , Virulence , Intestinal Mucosa , Metabolism , Microbiology , Pathology , Lung , Metabolism , Pathology , Male , Mice, Inbred BALB C , Orthomyxoviridae Infections , Drug Therapy , Pathology , Plant Extracts , Chemistry , Polysaccharides , Chemistry , Pharmacology , Therapeutic Uses , Toll-Like Receptors , Metabolism , Zonula Occludens-1 Protein , Metabolism
14.
Experimental Neurobiology ; : 352-361, 2019.
Article in English | WPRIM | ID: wpr-763769

ABSTRACT

Neuroinflammation is one of the key mechanisms of neuropathic pain, which is primarily mediated by the Toll-like receptor 4 (TLR4) signaling pathways in microglia. Therefore, TLR4 may be a reasonable target for treatment of neuropathic pain. Here, we examined the analgesic effect of TLR4 antagonistic peptide 2 (TAP2) on neuropathic pain induced by spinal nerve ligation in rats. When lipopolysaccharide (LPS)-stimulated BV2 microglia cells were treated with TAP2 (10 µM), the mRNA levels of proinflammatory mediators, such as tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-6, cyclooxygenase (COX)-2, and inducible nitric oxide synthase (iNOS), were markedly decreased by 54–83% as determined by quantitative PCR (qPCR) analysis. Furthermore, when TAP2 (25 nmol in 20 µL PBS) was intrathecally administered to the spinal nerve ligation-induced rats on day 3 after surgery, the mechanical allodynia was markedly decreased for approximately 2 weeks in von Frey filament tests, with a reduction in microglial activation. On immunohistochemical and qPCR analyses, both the level of reactive oxygen species and the gene expression of the proinflammatory mediators, such as TNF-α, IL-1β, IL-6, COX-2, and iNOS, were significantly decreased in the ipsilateral spinal dorsal horn. Finally, the analgesic effect of TAP2 was reproduced in rats with monoiodoacetate-induced osteoarthritic pain. The findings of the present study suggest that TAP2 efficiently mitigates neuropathic pain behavior by suppressing microglial activation, followed by downregulation of neuropathic pain-related factors, such as reactive oxygen species and proinflammatory molecules. Therefore, it may be useful as a new analgesic for treatment of neuropathic pain.


Subject(s)
Analgesics , Animals , Down-Regulation , Gene Expression , Hyperalgesia , Interleukin-6 , Interleukins , Ligation , Microglia , Neuralgia , Nitric Oxide Synthase Type II , Polymerase Chain Reaction , Prostaglandin-Endoperoxide Synthases , Rats , Reactive Oxygen Species , RNA, Messenger , Spinal Cord Dorsal Horn , Spinal Nerves , Toll-Like Receptor 4 , Toll-Like Receptors , Tumor Necrosis Factor-alpha
15.
Journal of Experimental Hematology ; (6): 1664-1671, 2019.
Article in Chinese | WPRIM | ID: wpr-775668

ABSTRACT

OBJECTIVE@#To detect the expression of serum HMGB1 and CD14 monocyte Toll-like receptors in children with hemophagocytic syndrome (HPS), and to analyze its effect on the prognosis of children.@*METHODS@#Eight-three children with HPS admitted in Department of pediatrics of Wuhan Children's Hospital Affiliated to Tongji Medical College of Huazhong University of Science and Technology were selected and enrolled in HPS group, at the same time 50 healthy children with same age were selected and enrolled in control group. The peripheral blood of children in 2 groups was collected. The flow cytometry was used to detect the expression of Toll-like receptors (TLR2, TLR4 and TLR6) in peripheral blood CD14 monocytes, the ELISA was used to detect the expression of HMGB1 in serum of peripheral blood. The relationship of TLR2, TLR4, TLR6 and HMGB1 expression with the clinical parameters, short-term therapentic efficacy and prognosis was analyzed, the relation of TLR2, TLR4 and TLR6 expression with HMGB1 also was analyzed.@*RESULTS@#The expression of TLR2, TLR4 and TLR6 on surface of CD14 monocytes and fluorescence intensity in HPS group were significantly higher than those in control group (P<0.05). The serum HMGB1 level in HPS group was significantly higher than that in control group (P<0.05). The expression levels of TLR2, TLR4, TLR6 and HMGB1 in HPS children who were in acute phase or had decrease of albumin or hemoglobin levels, thrombocytopenia, neutrophil absolute value to low and increase of triglycerides level, in HPS group all significantly increased, the difference in children with different sex and age was no statistically significant (P>0.05). After treatment, the expressions of TLR2, TLR4, TLR6 and HMGB in CR and NAD groups was significantly lower than that before treatment (P<0.05), while the expressions levels of TLR2, TLR4, TLR6 and HMGB in AD and RD groups were no statistically significant different from those before treatment (P<0.05); the expressions levels of TLR2, TLR4, TLR6 and HMGB in dealth group all were higher than those in survival group (P<0.05). The serum HMGB1 levels in HPS children positively correlated with expression of TLR2, TLR4 and TLR6 on CD14 monocytes (P< 0.05).@*CONCLUSION@#The expression rate and level of TLR2, TLR4 and TLR6 on CD14 monocytes in HPS children are significantly higher than those in healthy children.The expression levels of TLR2, TLR4, and TLR6 positively correlate with serum HMGB1 content, which provides reference for the diagnosis and prognosis of children with HPS.


Subject(s)
Child , HMGB1 Protein , Humans , Lymphohistiocytosis, Hemophagocytic , Monocytes , Prognosis , Toll-Like Receptors
16.
Article in English | WPRIM | ID: wpr-740301

ABSTRACT

Toll-like receptors (TLR) are well-characterized pattern recognition receptors that can recognize and respond to diverse pathogen-associated or danger-associated molecular patterns during infection. TLR signaling in macrophages triggers in the intracellular signaling pathways through the recruitment of various adaptor and signaling proteins, and results in the activation of effector mechanisms and pathways that are important for host defense to intracellular bacteria. Effector mechanisms include inflammatory responses, cytokine generation, production of reactive oxygen species, and antimicrobial proteins. Accumulating studies showed that autophagy is a key pathway in the maintenance of homeostasis and housekeeping functions during infection and inflammation. In this review, we summarize the major effector pathways and mechanisms in the activation of TLR-inducible innate immune responses in macrophages. In addition, we focus the emerging evidence of crosstalk between autophagy and TLR-mediated signaling in terms of effector function of innate immune responses. A better understanding of effector functions by the activation of TLR-mediated signaling cascades contributes to the development of new therapeutics and vaccines against various intracellular pathogenic infections.


Subject(s)
Autophagy , Bacteria , Homeostasis , Housekeeping , Immunity, Innate , Inflammation , Macrophages , Reactive Oxygen Species , Receptors, Pattern Recognition , Toll-Like Receptors , Vaccines
17.
Braz. j. med. biol. res ; 52(7): e8732, 2019. tab, graf
Article in English | LILACS | ID: biblio-1011598

ABSTRACT

Inflammation plays an important role in the development of cardiovascular diseases (CVDs), suggesting that the immune system is a target of therapeutic interventions used for treating CVDs. This study evaluated mechanisms underlying inflammatory response and cardiomyocyte hypertrophy associated with bacterial lipopolysaccharide (LPS)- or heat shock protein 60 (HSP60)-induced Toll-like receptor (TLR) stimulation and the effect of a small interfering RNA (siRNA) against Ca2+/calmodulin-dependent kinase II delta B (CaMKIIδB) on these outcomes. Our results showed that treatment with HSP60 or LPS (TLR agonists) induced cardiomyocyte hypertrophy and complement system C3 and factor B gene expression. In vitro silencing of CaMKIIδB prevented complement gene transcription and cardiomyocyte hypertrophy associated with TLR 2/4 activation but did not prevent the increase in interleukin-6 and tumor necrosis factor-alfa gene expression in primary cultured cardiomyocytes. Moreover, CaMKIIδB silencing attenuated nuclear factor-kappa B expression. These findings supported the hypothesis that CaMKIIδB acts as a link between inflammation and cardiac hypertrophy. Furthermore, the present study is the first to show that extracellular HSP60 activated complement gene expression through CaMKIIδB. Our results indicated that a stress stimulus induced by LPS or HSP60 treatment promoted cardiomyocyte hypertrophy and initiated an inflammatory response through the complement system. However, CaMKIIδB silencing prevented the cardiomyocyte hypertrophy independent of inflammatory response induced by LPS or HSP60 treatment.


Subject(s)
Animals , Rats , Myocytes, Cardiac/pathology , Toll-Like Receptors/metabolism , Calcium-Calmodulin-Dependent Protein Kinase Type 2/metabolism , Signal Transduction/physiology , Gene Expression , Lipopolysaccharides/pharmacology , NF-kappa B/metabolism , Rats, Wistar , Chaperonin 60/pharmacology , Myocytes, Cardiac/drug effects , Myocytes, Cardiac/metabolism , RNA, Small Interfering , Inflammation/metabolism
18.
Rev. Soc. Bras. Med. Trop ; 51(6): 725-730, Nov.-Dec. 2018. tab, graf
Article in English | LILACS | ID: biblio-977100

ABSTRACT

Abstract Invasive aspergillosis is a common fungal infection in immunocompromised individuals. Some studies have shown that toll-like receptor and dectin-1 genetic polymorphisms may alter signaling pathways, thus increasing an individual's susceptibility to invasive aspergillosis. We investigated the pertinent literature to determine whether polymorphisms in the genes encoding toll-like receptors and dectin-1 increase the susceptibility to invasive aspergillosis. This study systematically reviewed the literature using the databases PubMed/PMC, Scopus, and Web of Science using the keywords invasive aspergillosis, polymorphism, Toll-like, and Dectin-1. From the initial search, 415 studies were found and according to our inclusion and exclusion criteria, eight studies were selected. Several studies described single-nucleotide polymorphisms (SNPs) that are associated with a greater susceptibility to invasive aspergillosis. These SNPs were found in the genes that encode toll-like receptors 1, 3, 4, and 5 and the gene that encodes dectin-1; upon activation, both cellular receptors initiate a signaling cascade that can result in the production of cytokines and chemokines. Thus, our literature review uncovered a significant association between polymorphisms in the genes that encode toll-like receptors and dectin-1 and invasive aspergillosis. More studies should be performed to better understand the relationship between toll-like receptor and dectin-1 genetic polymorphisms and invasive aspergillosis susceptibility.


Subject(s)
Humans , Aspergillosis/genetics , Genetic Predisposition to Disease/genetics , Polymorphism, Single Nucleotide/genetics , Lectins, C-Type/genetics , Toll-Like Receptors/genetics
19.
An. bras. dermatol ; 93(2): 242-250, Mar.-Apr. 2018. tab, graf
Article in English | LILACS | ID: biblio-887186

ABSTRACT

Abstract: Skin's innate immunity is the initial activator of immune response mechanisms, influencing the development of adaptive immunity. Some contact allergens are detected by Toll-like receptors (TLRs) and inflammasome NLR3. Keratinocytes participate in innate immunity and, in addition to functioning as an anatomical barrier, secrete cytokines, such as TNF, IL-1β, and IL-18, contributing to the development of Allergic Contact Dermatitis. Dendritic cells recognize and process antigenic peptides into T cells. Neutrophils cause pro-inflammatory reactions, mast cells induce migration/maturation of skin DCs, the natural killer cells have natural cytotoxic capacity, the γδ T cells favor contact with hapten during the sensitization phase, and the innate lymphoid cells act in the early stages by secreting cytokines, as well as act in inflammation and tissue homeostasis. The antigen-specific inflammation is mediated by T cells, and each subtype of T cells (Th1/Tc1, Th2/Tc2, and Th17/Tc17) activates resident skin cells, thus contributing to inflammation. Skin's regulatory T cells have a strong ability to inhibit the proliferation of hapten-specific T cells, acting at the end of the Allergic Contact Dermatitis response and in the control of systemic immune responses. In this review, we report how cutaneous innate immunity is the first line of defense and focus its role in the activation of the adaptive immune response, with effector response induction and its regulation.


Subject(s)
Humans , Skin/immunology , T-Lymphocytes/immunology , Dermatitis, Allergic Contact/immunology , Immunity, Innate/immunology , Cytokines/immunology , T-Lymphocytes, Regulatory/immunology , Toll-Like Receptors/immunology
20.
Electron. j. biotechnol ; 31: 93-99, Jan. 2018. ilus, graf, tab
Article in English | LILACS | ID: biblio-1022150

ABSTRACT

Background: Peptidoglycan (PGN) recognition proteins (PGRPs) are important pattern recognition receptors of the host innate immune system that are involved in the immune defense against bacterial pathogens. PGRPs have been characterized in several fish species. The PGN-binding ability is important for the function of PGRPs. However, the PGRP-PGN interaction mechanism in fish remains unclear. In the present study, the 3-D model of a long PGRP of half-smooth tongue sole (Cynoglossus semilaevis) (csPGRP-L), a marine teleost with great economic value, was constructed through the comparative modeling method, and the key amino acids involved in the interaction with Lys-type PGNs and Dap-type PGNs were analyzed by molecular dynamics and molecular docking methods. Results: csPGRP-L possessed a typical PGRP structure, consisting of five ß-sheets and four α-helices. Molecular docking showed that the van der Waals forces had a slightly larger contribution than Coulombic interaction in the csPGRP-L-PGN complex. Moreover, the binding energies of csPGRP-L-PGNs computed by MM-PBSA method revealed that csPGRP-L might selectively bind both types of MTP-PGNs and MPP-PGNs. In addition, the binding energy of each residue of csPGRP-L was also calculated, revealing that the residues involved in the interaction with Lys-type PGNs were different from that with Dap-type PGNs. Conclusions: The 3-D structure of csPGRP-L possessed typical PGRP structure and might selectively bind both types of MTP- and MPP-PGNs, which provided useful insights to understanding the functions of fish PGRPs.


Subject(s)
Animals , Tongue/immunology , Flatfishes/immunology , Flatfishes/metabolism , Binding Sites , Flatfishes/genetics , Peptidoglycan , Carrier Proteins , Toll-Like Receptors , Molecular Dynamics Simulation , Molecular Docking Simulation , Ligands
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