
pmid: 20951669
TLR-4 has also been identified as a receptor for endogenous alarmins, which are increased post transplantation. TLR-4 has also been associated with a polymorphism that could impact graft outcome.To assess the expression of TLR-4 in kidney transplant patients carrying or not a polymorphism.TLR-4 polymorphism (A299G/T399I) was studied in 200 renal transplant patients. Healthy volunteers were also enrolled as control group. The polymorphism analysis was performed using restriction enzymes technique (RFLP). Functionality of TLR-4 polymorphism was assessed in samples from controls by quantification of TNF-α after LPS stimulus. TLR-4 and -2 expressions were also analyzed by flow cytometry.TLR-4 polymorphism was present in 8.5% of renal transplant patients. This polymorphism was associated with impairment in TNF-α secretion. In general, in renal transplant patients, TLR-4 expression in monocytes and in neutrophils was lower than in health volunteers. TLR-2 and TLR-4 expressions in healthy volunteers with A299G/T399I TLR-4 polymorphism was higher than in wild-type genotype healthy volunteers (p<0.01 and p<0.05, respectively), and also higher than A299G/T399I TLR-4 polymorphism renal transplant patients (p<0.05). TLR-2 expression on neutrophils in wild-type genotype renal transplant patients was higher compared to wild-type genotype healthy volunteers, and was also higher in relation to A299G/T399I kidney transplanted patients (p<0.01).Stable renal transplant patients with TLR-4 polymorphism have a lower expression of TLR-4 and TLR-2 receptors in peripheral mononuclear cells, which ultimately indicate a less responsiveness for alarmins.
Adult, Graft Rejection, Lipopolysaccharides, Male, Genotype, 610, Gene Expression, Enzyme-Linked Immunosorbent Assay, 616, TLR2, Humans, TLR4, Polymorphism, Kidney transplant, Cells, Cultured, Dose-Response Relationship, Drug, Tumor Necrosis Factor-alpha, Kidney Transplantation, Toll-Like Receptor 2, Toll-Like Receptor 4, Case-Control Studies, Leukocytes, Mononuclear, Female, Polymorphism, Restriction Fragment Length
Adult, Graft Rejection, Lipopolysaccharides, Male, Genotype, 610, Gene Expression, Enzyme-Linked Immunosorbent Assay, 616, TLR2, Humans, TLR4, Polymorphism, Kidney transplant, Cells, Cultured, Dose-Response Relationship, Drug, Tumor Necrosis Factor-alpha, Kidney Transplantation, Toll-Like Receptor 2, Toll-Like Receptor 4, Case-Control Studies, Leukocytes, Mononuclear, Female, Polymorphism, Restriction Fragment Length
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