Expression and function of Cbl-b in T cells from patients with systemic lupus erythematosus, and detection of the 2126 A/G Cblb gene polymorphism in the Mexican mestizo population
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Systemic lupus erythematosus (SLE) is characterized by abnormalities in the function of T and B lymphocytes and in the signaling pathways induced through their receptors. Cbl-b is an intracellular adaptor protein that plays a key role in the negative regulation of lymphocyte activity. We explored the expression and function of Cbl-b in T lymphocytes from SLE patients. In addition, the possible association of SLE and a single nucleotide polymorphism (SNP) of the Cblb gene was determined. We studied 150 SLE patients, 163 healthy individuals, and 14 patients with rheumatoid arthritis (RA). The expression of Cbl-b was analyzed in the peripheral blood mononuclear cells, and the negative regulatory function of Cbl-b was assessed by analyzing actin polymerization and the phosphorylation of JNK and c-Jun induced through CD3. Furthermore, the 2126(A/G) SNP of the Cblb gene was detected by real-time polymerase chain reaction. We found a significant small reduction in the expression of Cbl-b as well as increased levels of activation of c-Jun and actin polymerization in T lymphocytes from patients with SLE compared with healthy controls or RA patients. In addition, a significant association between the 2126(A/G) SNP and SLE was detected. Our data suggest that Cbl-b may contribute to the deregulated activation of T lymphocytes observed in SLE. © The Author(s), 2011.
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autoimmune diseases; Cbl-b; immunoregulation; intracellular signaling; T lymphocytes adaptor protein; CD3 antigen; protein cbl b; stress activated protein kinase; unclassified drug; actin polymerization; article; controlled study; enzyme activation; enzyme phosphorylation; genetic analysis; human; human cell; major clinical study; Mexico; peripheral blood mononuclear cell; priority journal; protein analysis; protein expression; real time polymerase chain reaction; regulatory mechanism; rheumatoid arthritis; single nucleotide polymorphism; systemic lupus erythematosus; T lymphocyte; T lymphocyte activation; Actins; Adaptor Proteins, Signal Transducing; Arthritis, Rheumatoid; Case-Control Studies; Humans; Leukocytes, Mononuclear; Lupus Erythematosus, Systemic; Mexico; Phosphorylation; Polymerase Chain Reaction; Polymerization; Polymorphism, Single Nucleotide; Proto-Oncogene Proteins c-cbl; Proto-Oncogene Proteins c-jun; T-Lymphocytes
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