Increased production of intracellular interleukin-1 receptor antagonist type I in the synovium of mice with collagen-induced arthritis: a possible role in the resolution of arthritis.

Increased production of intracellular interleukin-1 receptor antagonist type I in the synovium of mice with collagen-induced arthritis: a possible role in the resolution of arthritis.
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胶原诱导性关节炎小鼠滑膜中细胞内白细胞介素 1 受体拮抗剂 I 型的产生增加:可能在缓解关节炎中发挥作用。

DOI:
10.1002/1529-0131(200102)44:2
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发表时间:
2001
期刊:
Arthritis and rheumatism.
影响因子:
--
通讯作者:
Arend,WP
Arend,WP
中科院分区:
--
文献类型:
--
作者:
Gabay,C;Marinova-Mutafchieva,L;Williams,RO;Gigley,JP;Butler,DM;Feldmann,M;Arend,WP

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目的研究白细胞介素1受体拮抗剂(IL-1 Ra)和IL-1β在体内关节炎中的表达模式。方法用II型胶原免疫DBA/1小鼠诱导关节炎,通过逆转录聚合酶链反应(RT-PCR)、RNA酶保护试验、Western印迹、免疫组化染色、免疫组织化学等方法检测IL-1 Ra在关节和滑膜组织中的表达。和原位杂交。IL-1β的产生也使用类似的approaches. ResultsIL-1 Ra的生产增加在胶原诱导的关节炎(CIA)的关节。通过RT-PCR,在正常关节中检测到分泌的IL-1 Ra信使RNA(mRNA),而细胞内IL-1 Ra I型(icIL-1 Ra 1)mRNA仅在炎症关节中产生。蛋白质印迹研究表明,在CIA过程中,关节中的icIL-1 Ra 1蛋白水平增加,并且icIL-1 Ra 3蛋白也以少量存在。RNA酶保护试验表明,在关节炎的第14天,炎症关节中IL-1β:IL-1 Ra mRNA的比例增加,而在以后的时间点(从第20天到第60天)则出现相反的模式。与这一发现一致,免疫组织化学和原位杂交研究证实icIL-1 Ra 1仅存在于炎症关节中。CIA的组织学评价表明,在疾病的过程中,急性炎症的决议,因为icIL-1 Ra 1的生产增加和IL-1β的总IL-1Rareduced.ConclusionProduction的IL-1 Ra亚型,特别是icIL-1 Ra 1,刺激炎症关节在CIA小鼠。CIA过程中IL-1β产生减少和icIL-1 Ra 1水平升高的组合与炎症活动减少相关。这些结果表明icIL-1 Ra 1可能在小鼠CIA的消退中发挥作用。
ObjectiveTo examine the patterns of production of interleukin‐1 receptor antagonist (IL‐1Ra) isoforms and of IL‐1β during arthritis in vivo.MethodsArthritis was induced in DBA/1 mice by immunization with type II collagen, and the production of IL‐1Ra isoforms was examined in whole joints and in dissected synovial tissues by reverse transcription–polymerase chain reaction (RT‐PCR), RNase protection assay, Western blotting, immunostaining, and in situ hybridization. Production of IL‐1β also was examined using similar approaches.ResultsProduction of IL‐1Ra increased in the joints during collagen‐induced arthritis (CIA). By RT‐PCR, secreted IL‐1Ra messenger RNA (mRNA) was detected in normal joints, whereas intracellular IL‐1Ra type I (icIL‐1Ra1) mRNA was only produced in inflamed joints. Western blot studies showed that icIL‐1Ra1 protein levels increased in the joints during the course of CIA and that icIL‐1Ra3 protein was also present in low amounts. RNase protection assays showed that the IL‐1β:IL‐1Ra mRNA ratio was increased in inflamed joints through day 14 of arthritis, whereas a reverse pattern was present at later time points (from day 20 to day 60). Consistent with this finding, immunohistochemistry and in situ hybridization studies confirmed that icIL‐1Ra1 was only present in inflamed joints. The histologic evaluation of CIA during the course of the disease indicated a resolution of acute inflammation, since icIL‐1Ra1 production increased and the ratio of IL‐1β to total IL‐1Ra decreased.ConclusionProduction of IL‐1Ra isoforms, particularly icIL‐1Ra1, is stimulated in inflamed joints during CIA in mice. The combination of decreased production of IL‐1β and elevated levels of icIL‐1Ra1 during the course of CIA was associated with a reduction in inflammatory activity. These results suggest that icIL‐1Ra1 may play a role in the resolution of murine CIA.
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发表时间: 2000-01-17
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影响因子: --
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DOI: --
发表时间: 1993
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