Increased expression of c-rel, from the NF-?B/Rel family, in T cells from patients with systemic lupus erythematosus

Burgos P.; Bull, P; Metz, C; Pincheira, R; Massardo, L; Errazuriz, C; Jacobelli, S.; González A; Bono M.R.

Keywords: sequence, proteins, activation, expression, transcription, binding, protein, chloroquine, cell, gene, methylprednisolone, prednisone, chain, t-lymphocytes, humans, mononuclear, human, male, autoimmunity, polymerase, regulation, oncogene, aged, agent, c-rel, adult, female, rna, interleukin-2, article, child, factor, enhancer, adolescent, lupus, lymphocyte, immunoglobulin, erythematosus, systemic, nf-kappa, controlled, clinical, reverse, study, nucleotide, priority, middle, Reaction, journal, RNA,, a, Proto-Oncogene, Messenger, Erythematosus,, t, concanavalin, b, immunosuppressive, corticosteroid, Leukocytes,, proto


Objective. To explore the role of the NF-?B/Rel transcription factor family in autoimmunity, we investigated whether peripheral blood mononuclear cells (PBMC) and T cells from the blood of patients with systemic lupus erythematosus (SLE) exhibit abnormal expression of c-rel, both when recently isolated and/or during in vitro activation. Methods. Total RNA and protein extracts were prepared from PBMC and T cells isolated by immunoadsorption with magnetic beads. The relative concentrations of c-rel mRNA and of c-Rel protein were determined by semiquantitative assays of competitive reverse transcriptase-polymerase chain reaction and chemiluminescent immunoblots, respectively. Activity of NF-?B/Rel was studied by electrophoretic mobility shift assay of nuclear extracts. Results. Significantly increased levels of c-rel mRNA were found (1) in PBMC from SLE patients (n = 48; p < 0.0000001), even during inactive disease (n = 11; p < 0.001), compared to controls (n = 54), and (2) in T cells isolated from a subgroup of these patients (n = 11; p < 0.00002) and controls (n = 12). c-Rel protein was found increased in the cytosol but not in the nucleus of PBMC of patients with SLE (n = 12; p < 0.02) compared to controls (n = 12). No evidence of NF-?B/Rel nuclear activity was detected. In vitro stimulation of T cells by incubating PBMC with concanavalin A showed that less c-Rel entered the nucleus in lupus cells than healthy cells, correlating with lower interleukin 2 production. However, the same stimulating conditions provoked an increase in c-rel mRNA to higher levels in lupus cells from 2 patients compared with 2 controls. Increased levels of both I?B ? and I?B ? could account for c-Rel cytosolic retention. Conclusion. Our data suggest that T cells from patients with SLE possess altered regulatory mechanisms of c-rel expression and nuclear import that might potentially determine conditions for developing autoimmunity. Other cells present in the PBMC could also be affected.

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Título según SCOPUS: Increased expression of c-rel, from the NF-?B/Rel family, in T cells from patients with systemic lupus erythematosus
Volumen: 27
Número: 1
Fecha de publicación: 2000
Página de inicio: 116
Página final: 127
Idioma: English