A role for bradykinin in the development of anti-collagen antibody-induced arthritis.
A role for bradykinin in the development of anti-collagen antibody-induced arthritis.
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DOI：
10.1093/rheumatology/keu015
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发表时间：
2014-07
期刊：
影响因子：
5.5
通讯作者：
Zhanli Xie;J. Dai;Aizhen Yang;Yi Wu
中科院分区：
文献类型：
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作者：
Zhanli Xie;J. Dai;Aizhen Yang;Yi Wu
目的：临床和实验观察表明，缓激肽是血浆钾likrein-kinin系统的主要激活产物，参与关节炎的发病机制，但缓激肽受体的致病作用仍不确定。在这项研究中，我们使用双受体缺陷（B1RB2R(-/-)）小鼠研究了缓激肽受体在抗胶原抗体诱导的关节炎（CAIA）的发病机制中是否重要。方法在第0天和第3天分别通过注射抗胶原抗体鸡尾酒和脂多糖诱导B1RB2R（+/+）和B1RB2R（-/-）小鼠CAIA。通过测量关节直径和组织学分析来评估疾病的严重程度。采用ELISA和实时RT-PCR检测关节组织和外周单核细胞中促炎细胞因子的表达。结果RT-PCR证实B1RB2R（-/-）小鼠B1RB2R和B2R mRNA表达缺失。虽然B1RB2R（+/+）小鼠出现了严重的CAIA，但B1RB2R（-/-）小鼠的疾病严重程度显著减轻。在携带CAIA的B1RB2R（+/+）小鼠中，关节组织和外周单个核细胞中的B1R和B2R mRNA水平均升高。与B1RB2R（+/+）小鼠相比，B1RB2R（-/-）小鼠关节组织中IL-1β和IL-6的产生及外周单核细胞中IL-1β和IL-6 mRNA的表达均显著降低。结论迟缓激肽在CAIA发病机制中起重要作用。B1R在炎症关节组织和外周炎症细胞中诱导表达，在CAIA的发展中起重要作用。
OBJECTIVES Clinical and experimental observations have suggested that bradykinin, a major activation product of the plasma kallikrein-kinin system, is involved in the pathogenesis of arthritis, but the pathogenic role of bradykinin receptors remains inconclusive. In this study we examined whether bradykinin receptors are important in the pathogenesis of anti-collagen antibody-induced arthritis (CAIA) using double receptor-deficient (B1RB2R(-/-)) mice. METHODS CAIA was induced in B1RB2R(+/+) and B1RB2R(-/-) mice by injection of an anti-collagen antibody cocktail on day 0 and lipopolysaccharide on day 3. Severity of disease was evaluated by measurement of joint diameter and histological analysis. The expression of proinflammatory cytokines in joint tissue and peripheral mononuclear cells was determined by ELISA and real-time RT-PCR. RESULTS The absent expression of B1R and B2R mRNA in B1RB2R(-/-) mice was confirmed by RT-PCR. Although B1RB2R(+/+) mice developed severe CAIA, the severity of the disease was significantly attenuated in B1RB2R(-/-) mice. In B1RB2R(+/+) mice bearing CAIA, both B1R and B2R mRNA levels were increased in joint tissue and peripheral mononuclear cells. Compared with B1RB2R(+/+) mice, the production of IL-1β and IL-6 in joint tissue and their mRNA expression in peripheral mononuclear cells were remarkably reduced in B1RB2R(-/-) mice. CONCLUSION These observations provide genetic evidence that bradykinin plays an important role in the pathogenesis of CAIA. B1R, whose expression is induced in inflamed joint tissue and peripheral inflammatory cells, is important in the development of CAIA.