Expression and function of the P2X(7) purinergic receptor in patients with systemic lupus erythematosus and rheumatoid arthritis.
Because the synthesis of pro-inflammatory cytokines and apoptosis of lymphoid cells can be induced through P2X(7), we decided to study its expression, function (apoptosis, shedding of CD62L and synthesis of IL-1beta 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 P2X(7) 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-1beta upon stimulation with ATP was significantly decreased in SLE patients. In contrast, in RA patients we detected that the release of IL-1beta was increased. In addition, in patients with SLE and RA the SNPs 1513 AC was associated with a low expression of P2X(7). These results suggest a possible involvement of P2X(7) in the pathogenesis of inflammatory autoimmune diseases.
Portales-Cervantes
Liliana
L
Department of Immunology, Facultad de Medicina Universidad Autónoma de San Luis Potosí, México.
Niño-Moreno
Perla
P
Doníz-Padilla
Lesly
L
Baranda-Candido
Lourdes
L
García-Hernández
Mariana
M
Salgado-Bustamante
Mariana
M
González-Amaro
Roberto
R
Portales-Pérez
Diana
D
D000255:Adenosine Triphosphate / Q000494:pharmacology; D000293:Adolescent; D000328:Adult; D000368:Aged; D017209:Apoptosis / Q000187:drug effects; D001172:Arthritis, Rheumatoid / Q000097:blood / Q000235:genetics* / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D002478:Cells, Cultured; D017077:Culture Media, Conditioned / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005434:Flow Cytometry; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D053583:Interleukin-1beta / Q000378:metabolism; D019041:L-Selectin / Q000378:metabolism; D008180:Lupus Erythematosus, Systemic / Q000097:blood / Q000235:genetics* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D020641:Polymorphism, Single Nucleotide; D018048:Receptors, Purinergic P2 / Q000235:genetics* / Q000378:metabolism; D058486:Receptors, Purinergic P2X7; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D055815:Young Adult
D017077:Culture Media, Conditioned; D053583:Interleukin-1beta; C546468:P2RX7 protein, human; D018048:Receptors, Purinergic P2; D058486:Receptors, Purinergic P2X7; D014409:Tumor Necrosis Factor-alpha; D019041:L-Selectin; D000255:Adenosine Triphosphate