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Title: Expression of TLR-4 and -2 in peripheral mononuclear cells in renal transplant patients with TLR-4 gene polymorphism
Authors: Nogueira, Eliana [UNIFESP]
Salomao, Reinaldo [UNIFESP]
Collo Brunialti, Milena Karina [UNIFESP]
Ozaki, Kikumi S.
Marques, Georgia D. M.
Cenedeze, Marcos A.
Saraiva Camara, Niels Olsen
Pacheco-Silva, Alvaro
Universidade Federal de São Paulo (UNIFESP)
Universidade de São Paulo (USP)
Keywords: TLR4
Kidney transplant
Issue Date: 1-Dec-2010
Publisher: Elsevier B.V.
Citation: International Immunopharmacology. Amsterdam: Elsevier B.V., v. 10, n. 12, p. 1481-1485, 2010.
Abstract: Introduction: 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.Objective: To assess the expression of TLR-4 in kidney transplant patients carrying or not a polymorphism.Methods: 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-alpha after LPS stimulus. TLR-4 and -2 expressions were also analyzed by flow cytometry.Results: TLR-4 polymorphism was present in 8.5% of renal transplant patients. This polymorphism was associated with impairment in TNF-alpha 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).Conclusion: 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. (C) 2010 Elsevier B.V. All rights reserved.
ISSN: 1567-5769
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