Expression of TLR-4 and -2 in peripheral mononuclear cells in renal transplant patients with TLR-4 gene polymorphism

Autor(es)

Nogueira, Eliana ; Salomao, Reinaldo ; Collo Brunialti, Milena Karina ; Ozaki, Kikumi S. ; Marques, Georgia D. M. ; Cenedeze, Marcos A. ; Saraiva Camara, Niels Olsen ; Pacheco-Silva, Alvaro

• Tipo de documento: Artigo Científico
• Fonte: International Immunopharmacology; v. 10, n. 12, p. 5-pg., 2010-12-01.

Resumo

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. (AU)

• Processo FAPESP: 07/07139-3 - Investigando o papel da heme-oxigenase 1 em diferentes processos inflamatórios renais em modelos animais
• Beneficiário: Niels Olsen Saraiva Câmara
• Modalidade de apoio: Auxílio à Pesquisa - Temático
• Processo FAPESP: 07/08256-3 - Desenvolvimento de PCR em tempo real para detecção de resistência ao ganciclovir em pacientes transplantados renais com infecção persistente pelo citomegalovírus
• Beneficiário: Eliana Nogueira
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado