Expression and function of the P2X7 purinergic receptor in patients with systemic lupus erythematosus and rheumatoid arthritis
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Because the synthesis of pro-inflammatory cytokines and apoptosis of lymphoid cells can be induced through P2X7, we decided to study its expression, function (apoptosis, shedding of CD62L and synthesis of IL-1β induced by ATP) and genetic polymorphisms (1513 AC and -762 T/C) in peripheral blood mononuclear cells from 101 patients with systemic lupus erythematosus (SLE), 122 with rheumatoid arthritis (RA) and 90 healthy controls. We found no significant differences in the distribution of 1513 and -762 genotypes of P2X7 gene in SLE or RA patients compared with healthy controls. However, a diminished induction of apoptosis of CD4 T lymphocytes and monocytes was observed in SLE patients with the 1513 AC genotype, and the release of IL-1β upon stimulation with ATP was significantly decreased in SLE patients. In contrast, in RA patients we detected that the release of IL-1β was increased. In addition, in patients with SLE and RA the SNPs 1513 AC was associated with a low expression of P2X7. These results suggest a possible involvement of P2X7 in the pathogenesis of inflammatory autoimmune diseases. © 2010 American Society for Histocompatibility and Immunogenetics.
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Because the synthesis of pro-inflammatory cytokines and apoptosis of lymphoid cells can be induced through P2X7, we decided to study its expression, function (apoptosis, shedding of CD62L and synthesis of IL-1β induced by ATP) and genetic polymorphisms (1513 AC and -762 T/C) in peripheral blood mononuclear cells from 101 patients with systemic lupus erythematosus (SLE), 122 with rheumatoid arthritis (RA) and 90 healthy controls. We found no significant differences in the distribution of 1513 and -762 genotypes of P2X7 gene in SLE or RA patients compared with healthy controls. However, a diminished induction of apoptosis of CD4%2b T lymphocytes and monocytes was observed in SLE patients with the 1513 AC genotype, and the release of IL-1β upon stimulation with ATP was significantly decreased in SLE patients. In contrast, in RA patients we detected that the release of IL-1β was increased. In addition, in patients with SLE and RA the SNPs 1513 AC was associated with a low expression of P2X7. These results suggest a possible involvement of P2X7 in the pathogenesis of inflammatory autoimmune diseases. © 2010 American Society for Histocompatibility and Immunogenetics.
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Apoptosis; Autoimmunity; CD62L; IL-1β; P2X7 receptor; SNPs adenosine triphosphate; interleukin 1beta; L selectin; purinergic P2X7 receptor; tumor necrosis factor alpha; adolescent; adult; aged; apoptosis; article; CD4 T lymphocyte; controlled study; cytokine release; female; gene frequency; gene locus; genotype; human; human cell; immunostimulation; major clinical study; male; monocyte; peripheral blood mononuclear cell; polymerase chain reaction; priority journal; protein expression; receptor gene; restriction fragment length polymorphism; rheumatoid arthritis; single nucleotide polymorphism; systemic lupus erythematosus; Adenosine Triphosphate; Adolescent; Adult; Aged; Apoptosis; Arthritis, Rheumatoid; CD4-Positive T-Lymphocytes; Cells, Cultured; Culture Media, Conditioned; Enzyme-Linked Immunosorbent Assay; Female; Flow Cytometry; Gene Frequency; Genotype; Humans; Interleukin-1beta; L-Selectin; Lupus Erythematosus, Systemic; Male; Middle Aged; Monocytes; Polymorphism, Single Nucleotide; Receptors, Purinergic P2; Tumor Necrosis Factor-alpha; Young Adult
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Apoptosis; Autoimmunity; CD62L; IL-1β; P2X7 receptor; SNPs adenosine triphosphate; interleukin 1beta; L selectin; purinergic P2X7 receptor; tumor necrosis factor alpha; adolescent; adult; aged; apoptosis; article; CD4+ T lymphocyte; controlled study; cytokine release; female; gene frequency; gene locus; genotype; human; human cell; immunostimulation; major clinical study; male; monocyte; peripheral blood mononuclear cell; polymerase chain reaction; priority journal; protein expression; receptor gene; restriction fragment length polymorphism; rheumatoid arthritis; single nucleotide polymorphism; systemic lupus erythematosus; Adenosine Triphosphate; Adolescent; Adult; Aged; Apoptosis; Arthritis, Rheumatoid; CD4-Positive T-Lymphocytes; Cells, Cultured; Culture Media, Conditioned; Enzyme-Linked Immunosorbent Assay; Female; Flow Cytometry; Gene Frequency; Genotype; Humans; Interleukin-1beta; L-Selectin; Lupus Erythematosus, Systemic; Male; Middle Aged; Monocytes; Polymorphism, Single Nucleotide; Receptors, Purinergic P2; Tumor Necrosis Factor-alpha; Young Adult
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