Human rheumatoid synoviocytes express functional P2X7 receptors

被引：49

作者：

Caporali, Francesca ^{[1
]}

Capecchi, Pier Leopoldo ^{[1
]}

Gamberucci, Alessandra ^{[2
]}

Lazzerini, Pietro Enea ^{[1
]}

Pompella, Gerarda ^{[1
]}

Natale, Mariarita ^{[1
]}

Lorenzini, Sauro ^{[3
]}

Selvi, Enrico ^{[3
]}

Galeazzi, Mauro ^{[3
]}

Pasini, Franco Laghi ^{[1
]}

机构：

[1] Univ Siena, Policlin Le Scotte, Clin Immunol Sect, Dept Clin Med & Immunol Sci, I-53100 Siena, Italy

[2] Univ Siena, Dept Pathophysiol Expt Med & Publ Hlth, I-53100 Siena, Italy

[3] Univ Siena, Dept Clin Med & Immunol Sci, Rheumatol Sect, I-53100 Siena, Italy

来源：

JOURNAL OF MOLECULAR MEDICINE-JMM | 2008年 / 86卷 / 08期

关键词：

synoviocytes; P2X(7) receptors; IL-6; rheumatoid arthritis;

D O I：

10.1007/s00109-008-0365-8

中图分类号：

Q3 [遗传学];

学科分类号：

071007 [遗传学]; 090102 [作物遗传育种];

摘要：

Human type B synoviocytes are involved in joint injury during rheumatic diseases by producing inflammatory mediators such as interleukin-6 (IL-6). The increased level of purine and pirimidine nucleotides in the synovial fluid of rheumatoid arthritis (RA) patients could activate the large family of P2 receptors. Thus, we investigated the presence of P2 receptors in human type B synoviocytes from rheumatoid joints, also evaluating whether the P2X(7) receptor is involved in IL-6 release. Reverse transcriptase polymerase chain reaction analysis revealed messenger ribonucleic acid (mRNA) expression for the P2X(1), P2X(2), P2X(4), P2X(5), P2X(6), P2X(7), P2Y(1), P2Y(4), P2Y(11), P2Y(12), P2Y(13), and P2Y(14) but not the P2X(3), P2Y(2), and P2Y(6) receptors. The expression of the P2X(7) receptor was confirmed by Western blot analysis. Adenosine triphosphate (ATP) and the P2X(7) receptor agonist 2'-3'-O-(4-benzoylbenzoyl)ATP (BzATP) triggered an increase in intracellular calcium, thereby suggesting the expression of functional P2 receptors, including the P2X(7) receptor. Moreover, BzATP treatment upregulated both IL-6 mRNA and protein expression. Synoviocytes spontaneously released low quantities of IL-6; the incubation with BzATP induced the release of larger amounts of the cytokine, and such a release was blunted by the P2X(7) antagonist oxidized ATP. The selective P2X(1) and P2X(3) receptor agonist alpha,beta-methylene ATP did not affect IL-6 release. Finally, BzATP failed to induce a significant uptake of the large-molecule YO-PRO, thus suggesting the lack of pore formation after P2X(7) receptor stimulation. In conclusion, among the different P2 receptors expressed on human RA type B synoviocytes, the P2X(7) receptor may modulate IL-6 release but not inducing changes in cell membrane permeability.

引用

页码：937 / 949

页数：13

共 36 条

[1]

International union of pharmacology LVIII: Update on the P2Y G protein-coupled nucleotide receptors: From molecular mechanisms and pathophysiology to therapy [J].