Serum amyloid A (SAA) induces pentraxin 3 (PTX3) production in rheumatoid synoviocytes

Serum amyloid A (SAA) induces pentraxin 3 (PTX3) production in rheumatoid synoviocytes
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DOI:
10.1007/s10165-012-0630-0
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发表时间:
2013-01-01
影响因子:
2.2
通讯作者:
Migita, Kiyoshi
Migita, Kiyoshi
中科院分区:
医学3区
文献类型:
--
作者:
Satomura, Kenshi;Torigoshi, Takafumi;Migita, Kiyoshi

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正五聚蛋白3(PTX 3)是一种急性期反应物,参与炎症反应和先天免疫的放大。本研究采用逆转录聚合酶链反应(RT-PCR)和酶联免疫吸附试验(ELISA)检测PTX 3和血清淀粉样蛋白A(SAA)在类风湿关节炎滑膜细胞中的表达,探讨PTX 3与SAA的关系。SAA诱导的PTX 3表达减弱时,类风湿性滑膜细胞与N-甲酰肽受体配体-1(FPRL-1)特异性siRNA的核转染,表明FPRL-1的参与。此外,SAA诱导的PTX 3表达被NF-κ B或丝裂原活化蛋白激酶特异性抑制剂抑制。可溶性TNF受体(依那西普)和重组IL-1受体拮抗剂均不影响SAA刺激的滑膜细胞产生PTX 3,表明SAA直接诱导PTX 3。我们的数据表明SAA通过诱导PTX 3在类风湿滑膜的促炎和免疫反应中起作用。我们提供了第一个证据,证明由肝细胞全身产生的急性期反应物SAA通过在类风湿性滑液组织中局部诱导另一种促炎分子PTX 3来维持类风湿性炎症过程。
Pentraxin 3 (PTX3) is an acute-phase reactant that is involved in amplification of the inflammatory response and innate immunity. In the present study, we evaluated the relationship between PTX3 and serum amyloid A (SAA), another acute-phase reactant, in rheumatoid synoviocytes.PTX3 mRNA expression was examined by reverse transcription polymerase chain reaction, and PTX3 protein was measured by enzyme-linked immunosorbent assay.SAA induced PTX3 mRNA and PTX3 protein expression in rheumatoid synoviocytes. SAA-induced PTX3 expression was attenuated when rheumatoid synoviocytes were nucleofected with N-formyl peptide receptor ligand-1 (FPRL-1)-specific siRNA, suggesting the involvement of FPRL-1. Furthermore, SAA-induced PTX3 expression was inhibited by NF-kappa B or mitogen-activated protein kinase-specific inhibitors. Neither soluble TNF receptor (etanercept) nor recombinant IL-1 receptor antagonist affected PTX3 production by SAA-stimulated synoviocytes, suggesting that SAA directly induces PTX3.Our data suggest that SAA plays a role in the proinflammatory and immune responses in rheumatoid synovium by inducing PTX3. We provide the first evidence that the acute-phase reactant SAA, which is produced systemically by hepatocytes, perpetuates the rheumatoid inflammatory processes by inducing another proinflammatory molecule, PTX3, locally in rheumatoid synovial tissues.