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1.
Inflammation ; 35(3): 935-43, 2012 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-22009442

RESUMEN

Forty-two patients with systemic lupus erythematosus (SLE), including 26 patients with renal damage and 16 without, and 20 healthy controls were included in the study. The isolated peripheral blood mononuclear cells (PBMCs) were treated with a p38 inhibitor (SB203580) or anti-tumor necrosis factor-like weak inducer of apoptosis (TWEAK) mAb, with or without phytohemagglutinin/phorbol myristate acetate (PHA/PMA) stimulation. Western blot experiments were used to evaluate the protein expression of TWEAK and p38 MAPK in PBMCs .Next, the contents of interleukin-10 (IL-10) and monocyte chemoattractant protein-1 (MCP-1) in the supernatant were measured by ELISA. The results showed that expression of TWEAK protein in PBMCs from lupus nephritis patients was significantly higher than that from SLE patients without renal damage and healthy controls. PHA/PMA simulation could upregulate the productions of TWEAK and p-p38MAPK in PBMCs from patients with SLE. Anti-TWEAK mAb treatment downregulated both TWEAK and p-p38 MAPK expression in PBMCs, as well as IL-10 and MCP-1 in the supernatant; SB203580 had the same effect on cytokine production in PBMC, but had no effect on the expression of TWEAK. Our results suggested that TWEAK-p38 MAPK-IL-10, MCP-1 signaling pathway in PBMC played an important pathogenic role in lupus nephritis.


Asunto(s)
Leucocitos Mononucleares/metabolismo , Lupus Eritematoso Sistémico/metabolismo , Nefritis Lúpica/metabolismo , Receptores del Factor de Necrosis Tumoral/metabolismo , Factores de Necrosis Tumoral/metabolismo , Proteínas Quinasas p38 Activadas por Mitógenos/metabolismo , Adolescente , Adulto , Anticuerpos Monoclonales/inmunología , Células Cultivadas , Quimiocina CCL2/metabolismo , Femenino , Humanos , Imidazoles/farmacología , Imidazoles/uso terapéutico , Interleucina-10/metabolismo , Lupus Eritematoso Sistémico/sangre , Lupus Eritematoso Sistémico/inmunología , Nefritis Lúpica/sangre , Nefritis Lúpica/inmunología , Sistema de Señalización de MAP Quinasas , Masculino , Persona de Mediana Edad , Fitohemaglutininas/farmacología , Piridinas/farmacología , Piridinas/uso terapéutico , Receptores del Factor de Necrosis Tumoral/inmunología , Receptor de TWEAK , Acetato de Tetradecanoilforbol/farmacología , Factores de Necrosis Tumoral/inmunología , Adulto Joven , Proteínas Quinasas p38 Activadas por Mitógenos/antagonistas & inhibidores
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