No abstract available.
Kidney Diseases* ; Obesity* ; Toll-Like Receptor 4*

Organ transplant has become one of the strategies for treatment of malignant disease. The transplant-related complications restricted the further development of organ transplantation; graft rejection is most prominent among these complications, which remains a major cause of morbidity and mortality after organ transplant. Toll like receptors 4 (TLR-4) has been shown as a key molecule in innate immunity and immune tolerance. The role of TLR4 in graft rejection after organ transplant is still unknown. This article will review the role and the mechanism of TLR4 to control APC mature, activate T cells, trigger immune attack to organ graft; therefore bring new insights into the pathophysiology of graft rejection and foster the development of new therapies to control graft rejection after organ transplant.
Graft Rejection ; immunology ; Humans ; Toll-Like Receptor 4 ; immunology

To investigate the expression of Toll-like receptor (TLR) 2 and 4 mRNA in local tissues of model of oropharyngeal candidiasis in mice and to explore the potential role of TLR2 and TLR4 in earlier period of immune response, a murine model of oropharyngeal candidiasis inoculated by cotton wool balls saturated with Candida albicans was established. Mice were sacrificed at the indicated time points and the oropharyngeal tissues were excised. The expression of TLR2 and TLR4 mRNA was detected by RT-PCR. The results showed that low level of TLR2/4 mRNA could be detected in oropharyngeal tissues, but they were markedly up-regulated 6 h after inoculation, peaking after 12-24 h. Tissue TLR4 mRNA was gradually down-regulated 24-48 h, while TLR2 mRNA levels remained high up to the 72nd h. These data suggested that oropharyngeal infection of Candida albicans could result in up-regulation of TLR2/4 mRNA expression in local tissues, which might play important roles in earlier period of immune response.
Candidiasis/metabolism ; Candidiasis, Oral/*metabolism ; Mouth Mucosa/*metabolism ; Pharyngitis/metabolism ; RNA, Messenger/biosynthesis ; RNA, Messenger/genetics ; Random Allocation ; Toll-Like Receptor 2/*biosynthesis ; Toll-Like Receptor 2/genetics ; Toll-Like Receptor 4/*biosynthesis ; Toll-Like Receptor 4/genetics

Activation pattern recognition receptors can cause the startup of downstream signaling pathways, the expression of inflammatory factors, and finally immunological inflammatory reaction. Either exogenous pathogenic microorganisms or endogenous tissue components can activate these pattern recognition receptors as ligands at varying degrees, and then cause the immunological inflammatory reaction. Therefore, it is of great significance to inhibit relevant receptors, as well as the immunological inflammatory reaction, in order to avoid tissue injury during the course of disease. Baicalin is able to specifically inhibit the expression of TLR2/4-NOD2, inhibit the expression of inflammatory factors IL-1beta, IL-6 and TNF-alpha, and thereby reducing the injury of the tissue cells during the course of disease. This effect is non-specific with tissues, which is of great theoretical and practical significance in druggability. In addition, the drug metabolism and toxicity of baicalin are also discussed for its druggability in this article.
Animals ; Flavonoids ; pharmacology ; Humans ; Nod2 Signaling Adaptor Protein ; metabolism ; Toll-Like Receptor 2 ; metabolism ; Toll-Like Receptor 4 ; metabolism

OBJECTIVEThe aim of this study was to survey the influence of Toll-like receptor 2 (TLR2) and Toll-like receptor 4 (TLR4) repression to receptor activator of nuclear factor-kappaB ligand (RANKL) expression of human periodontal ligament fibroblasts (HPDLFs) under the stimulation of lipopolysaccharide (LPS).

METHODSThe level of RANKL in HPDLFs stimulated by 100 ng x mL(-1), 1 microg x mL(-1) and 10 microg x mL(-1) Escherichia coli (E. coli) LPS after 6, 12, 24 and 48 h was detected by enzyme linked immunosorbent assay (ELISA). The level of RANKL in HPDLFs stimulated by 1 microg x mL(-1) E. coli LPS after pretreatment with different titre anti-TLR2+anti-TLR4, anti-TLR2 and anti-TLR4 antibody were observed respectively.

RESULTSRANKL was detected at 6 h after stimulation with LPS, and the levels of these cytokine were highest at 24 h, and then gradually decreased. The regularity of each LPS concentration was approximately similar. After pretreatment with anti-TLR2+anti-TLR4, anti-TLR2 and anti-TLR4 antibody, the level of RANKL was significantly decreased under the stimulation of 1 microg x mL(-1) LPS (P<0.05). In the three groups, the expression of RANKL was significantly different (P<0.05). The level of RANKL in anti-TLR2+anti-TLR4 antibody pretreatment group was the lowest, the level in anti-TLR4 antibody pretreatment group was higher, and the level in anti-TLR2 antibody pretreatment group was the highest.

CONCLUSIONTLR2 and TLR4 participate in the process of RANKL expres-in HPDLFs induced by LPS. Anti-TLR4 antibody has better inhibition effect to RANKL expression of HPDLFs stimulated by LPS than anti-TLR2.

Escherichia coli ; Fibroblasts ; Humans ; Lipopolysaccharides ; Periodontal Ligament ; RANK Ligand ; Toll-Like Receptor 2 ; Toll-Like Receptor 4

OBJECTIVE: The aim of this study was to clarify whether stimulation of recombinant IL-17, TLR2 and TLR4 by their specific ligands induces the production of RANKL and IL-6 in the fibroblast-like synoviocytes (FLSs) from RA patients. METHODS: FLSs were isolated from RA synovial tissues and they were stimulated with the IL-17, TLR2 ligand bacterial peptidoglycan (PGN) and TLR4 ligand lipopolysaccharide (LPS). The RANKL levels were assessed by RT-PCR and western blotting. The expressions of IL-17, TLR2, TLR4, RANKL and IL-6 in the RA synovium were quantified by immunohistochemistry and these values were compared with the values obtained in the osteoarthritis synovium. The increased IL-6 production in the culture supernatants of the RA FLSs was quantified by sandwich ELISA. RESULTS: The mRNA and protein levels of RANKL and IL-6 increased in the RA FLSs stimulated with PGN, LPS and IL-17, or PGN plus IL-17 or LPS plus IL-17. The expressions of IL-17, TLR2, TLR4, RANKL and IL-6 were much higher in the RA synovium than those in the osteoarthritis (OA) synovium. CONCLUSION: We observed synergistic effects of TLR-2, TLR-4 and IL-17 upon the induction of RANKL. In conclusion, our data supports the previous evidence of an important role of TLR-2, TLR-4 and IL-17 in the pathogenesis of RA.
Blotting, Western ; Fibroblasts ; Humans ; Immunohistochemistry ; Interleukin-17 ; Interleukin-6 ; Ligands ; Osteoarthritis ; Peptidoglycan ; RNA, Messenger ; Synovial Membrane ; Toll-Like Receptor 2 ; Toll-Like Receptor 4 ; Toll-Like Receptors

Lipopolysaccharide (LPS), a main constituent of Gram-negative bacterial membrane, specifically activates Toll-like receptor 4, leading to the production of pleiotropic cytokines/chemokines which in turn regulate inflammatory and innate and subsequent adaptive immune responses. Given that human gut harbors a large collection of commensal bacteria, LPS released by gut microbes is able to make the great impact on gut homeostasis through the intracellular signaling pathways engaged by host-microbial interaction. Emerging evidence indicates that LPS in the gut has a potency to elicit the pathogenesis of intestinal inflammatory diseases such as inflammatory bowel disease and necrotizing enterocolitis. In this review, we discuss the current understanding of the basic biochemistry of LPS, LPS-induced intracellular signaling, and physiological impacts of LPS in the intestine.
Bacteria ; Biochemistry* ; Enterocolitis, Necrotizing ; Homeostasis ; Humans ; Inflammatory Bowel Diseases ; Intestines ; Lipopolysaccharides ; Membranes ; Toll-Like Receptor 4 ; Toll-Like Receptors

BACKGROUNDThe Toll-like receptors (TLRs) represent a group of single-pass transmembrane receptors expressed on sentinel cells that are central to innate immune responses.The aim of this study was to investigate the presence of soluble TLRs in pleural effusions, and the diagnostic values of TLRs for pleural effusion with various etiologies.

METHODSPleural effusion and serum samples were collected from 102 patients (36 with malignant pleural effusion, 36 with tuberculous pleural effusion, 18 with bacterial pleural effusion, and 12 with transudative pleural effusion). The concentrations of TLR1 to TLR10 were determined in effusion and serum samples by enzyme linked immunosorbent assay. Four classical parameters (protein, lactate dehydrogenase, glucose and C-reactive protein (CRP)) in the pleural fluid were also assessed. Receiver-operating characteristic curves were used to assess the sensitivity and specificity of pleural fluid TLRs and biochemical parameters for differentiating bacterial pleural effusion.

RESULTSThe concentrations of TLR1, TLR3, TLR4, TLR7 and TLR9 in bacterial pleural effusion were significantly higher than those in malignant, tuberculous, and transudative groups, respectively. Analysis of receiver operating characteristic curves revealed that the area under the curves of TLR1, TLR3, TLR4, TLR7 and TLR9 were 0.831, 0.843, 0.842, 0.883 and 0.786, respectively, suggesting that these TLRs play a role in the diagnosis of bacterial pleural effusion. Also, the diagnostic value of TLRs for bacterial pleural effusions was much better than that of biochemical parameters (protein, lactate dehydrogenase, glucose and CRP).

CONCLUSIONSThe concentrations of TLR1, TLR3, TLR4, TLR7 and TLR9 appeared to be increased in bacterial pleural effusion compared to non-bacterial pleural effusions. Determination of these pleural TLRs may improve the ability of clinicians to differentiate pleural effusion patients of bacterial origin from those with other etiologies.

Adolescent ; Adult ; Aged ; Aged, 80 and over ; Bacterial Infections ; metabolism ; Enzyme-Linked Immunosorbent Assay ; Female ; Humans ; Male ; Middle Aged ; Pleural Effusion ; metabolism ; microbiology ; Prospective Studies ; Toll-Like Receptor 1 ; metabolism ; Toll-Like Receptor 3 ; metabolism ; Toll-Like Receptor 4 ; metabolism ; Toll-Like Receptor 7 ; metabolism ; Toll-Like Receptor 9 ; metabolism ; Toll-Like Receptors ; metabolism ; Young Adult

Activation of microglia plays a vital role in the initiation and maintenance of specific neuropathic pain states. By activating microglia in central nervous system, Toll-like receptor 4 (TLR4) can promote the release of proinflammatory cytokines and neuroactive compounds, participate in the initiation and maintenance of neuropathic pain, and trigger the opiate side effects. Therefore, TLR4 may be a potential therapeutic target for neuropathic pain. Inhibition of TLR4 has shown some biological effects in neuropathic pain models and ibudilast (the TLR4 pathway-inhibiting agent) has been approved for for phase 2 clinical trials. This article briefly reviews the structure, function, and mechanism of TLR4 as well as the development of TLR4-targeted drugs.
Humans ; Neuralgia ; drug therapy ; physiopathology ; Toll-Like Receptor 4 ; antagonists & inhibitors ; physiology

OBJECTIVETo examine the role of lactoferrin (LF) on Toll like receptor 4 (TLR4) stimulated by lipopolysaccharide (LPS) in human periodontal ligament cells (hPDLCs).

METHODSPrimary hPDLCs were cultured by tissue block enzymolytic method. Cells obtained from four passages were identified and used in this experiment. Cells without stimulation served as the controls and cells treated with LPS (0.1 microg x mL(-1)) comprised the LPS group. The LPS + LF group was pretreated with LPS (0.1 microg x mL(-1)) for 2 h, and then treated with LF (10 microg x mL(-1)). Four hours after LF stimulation, the mRNA expression levels of TLR4 were examined by real-time quantitative polymerase chain reaction (RT-PCR). The protein expression of TLR4 was observed by cell immunofluorescence staining after LF stimulation of 24 hours.

RESULTSTLR4 mRNA expression in the LPS + LF group was significantly more decreased than that in the LPS group (P < 0.05), but exhibited no difference with that in the control group (P > 0.05). Cell immunofluorescence staining showed that the protein expression of TLR4 in the LPS + LF group was significantly more decreased than that in the LPS group (P < 0.05), but exhibited no difference with that in the control group (P > 0.05).

CONCLUSIONLF can decrease the expression of TLR4 stimulated by LPS in hPDLCs, thus presenting potential application for controlling the TLR4 immune pathway of periodontitis.

Down-Regulation ; Humans ; Lactoferrin ; Lipopolysaccharides ; Periodontal Ligament ; Periodontitis ; Toll-Like Receptor 4