Dynamics of proinflammatory cytokine expression in the joints of mice with collagen-induced arthritis (CIA)

Dynamics of proinflammatory cytokine expression in the joints of mice with collagen-induced arthritis (CIA)
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DOI:
10.1046/j.1365-2249.1997.2901181.x
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发表时间:
1997-03-01
影响因子:
4.6
通讯作者:
Maini, RN
Maini, RN
中科院分区:
医学3区
文献类型:
--
作者:
MarinovaMutafchieva, L;Williams, RO;Maini, RN

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这份报告包含了一个描述的细胞定位和动力学的促炎细胞因子的表达在小鼠CIA,类风湿性关节炎的模型。在临床关节炎发作后1-10天,取II型胶原免疫DBA/1小鼠未脱钙爪的组织冷冻切片,使用间接免疫过氧化物酶技术检查肿瘤坏死因子-α(TNF-α)、IL-1 β和IL-6的存在。与此同时,淋巴结细胞产生干扰素-γ(IFN-γ),在体外刺激11型胶原蛋白,作为T细胞活性的标志物进行了评估。TNF-α、IL-1 β和IL-6表达的主要区域在滑膜衬里层和软骨和骨(边缘区)邻接的组织中,特别是在血管翳形成和关节侵蚀部位。从关节炎的第1天到第10天,TNF-α、IL-1 β和IL-6阳性细胞的数量逐渐增加,在此期间,引流淋巴结的CD 4(+)T细胞产生的IFN-γ急剧下降。具有潜在意义的进一步发现是在关节炎的第1天一致地检测到TNF-α,而直到第3天才发现IL-1 β阳性细胞,这表明TNF-α的表达先于IL-1 β的表达。
This report contains a description of the cellular localization and kinetics of proinflammatory cytokine expression in murine CIA, a model for rheumatoid arthritis. Tissue cryostat sections of undecalcified paws from type II collagen-immunized DBA/1 mice, taken 1-10 days after the onset of clinical arthritis, were examined for the presence of tumour necrosis factor-alpha (TNF-alpha), IL-1 beta and IL-6 using an indirect immunoperoxidase technique. In parallel, interferon-gamma (IFN-gamma) production by lymph node cells, stimulated in vitro with type 11 collagen, was assessed as a marker of T cell activity. The main areas of TNF-alpha, IL-1 beta and IL-6 expression were in the synovial lining layer and in tissue contiguous with cartilage and bone (the marginal zone), in particular at sites of pannus formation and joint erosion. There was a progressive increase in the number of TNF-alpha-, IL-1 beta- and IL-6-positive cells from day 1 to day 10 of arthritis, during which time IFN-gamma production by CD4(+) T cells from draining lymph nodes declined sharply. A further finding of potential significance was that TNF-ol was consistently detected at day 1 of arthritis, whereas IL-1 beta-positive cells were not found until day 3, suggesting that the expression of TNF-alpha precedes that of IL-1 beta.