Mycoplasma bovis induces matrix metalloproteinase-3 expression in bovine synovial cells via up-regulation of interleukin-1β expression in mononuclear cells
Mycoplasma bovis induces matrix metalloproteinase-3 expression in bovine synovial cells via up-regulation of interleukin-1β expression in mononuclear cells
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DOI：
10.1016/j.vetimm.2020.110057
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发表时间：
2020-09-01
影响因子：
1.8
通讯作者：
Higuchi, Hidetoshi
中科院分区：
文献类型：
--
作者：
Nishi, Koji;Gondaira, Satoshi;Higuchi, Hidetoshi
牛支原体引起小牛慢性关节炎，表现为受累关节的骨质溶解。基质金属蛋白酶-3（MMP-3）是一种参与软骨降解的酶，由滑膜细胞产生。这种蛋白酶的产生受单核细胞产生的白细胞介素（IL）-1 β调节。已知这两种因子在人类自身免疫性关节炎和细菌性关节炎的骨质溶解中起重要作用。然而，支原体关节炎（MA）的病理生理学尚未阐明。在这项研究中，我们评估了MMP-3和IL-1 β在关节炎小牛滑液（SF）中的水平，并研究了IL-1 β对体外牛滑膜细胞MMP-3表达的影响。MA犊牛SF中MMP-3和IL-1 β的水平显著高于临床健康犊牛。与未暴露于牛支原体的细胞相比，牛支原体诱导单个核细胞中IL-1 β mRNA和蛋白的表达显著增加。牛有趣的是，M. Bovis含有高水平的IL-1 β，其诱导滑膜细胞MMP-3 mRNA和蛋白的表达高于M.牛重组牛IL-1 β还诱导滑膜细胞中MMP-3 mRNA和蛋白表达增加。结果表明，M. bovis诱导牛单核细胞表达IL-1 β，然后这种细胞因子促进滑膜细胞产生MMP-3。这些发现表明，MMP-3和IL-1 β是MA小牛骨质溶解发生的关键因素。
Mycoplasma bovis causes chronic arthritis in calves, presenting as osteolysis in affected joints. Matrix metalloproteinase-3 (MMP-3), an enzyme involved in cartilage degradation, is produced by synovial cells. Production of this proteinase is regulated by interleukin (IL)-1 beta, which is produced by mononuclear cells. Both factors are known to play important roles in osteolysis in human autoimmune and bacterial arthritis. However, the pathophysiology of Mycoplasma arthritis (MA) has not been elucidated. In this study, we evaluated the levels of MMP-3 and IL-1 beta in synovial fluid (SF) from MA calves and examined the effect of IL-1 beta on MMP-3 expression in bovine synovial cells in vitro. Levels of MMP-3 and IL-1 beta in SF from MA calves were significantly higher than those of clinically healthy calves. Mycoplasma bovis induced significant increases in the expression of IL-1 beta mRNA and protein in mononuclear cells, compared with cells not exposed to M. bovis. Interestingly, the supernatant of mononuclear cells stimulated with M. bovis contained high levels of IL-1 beta, which induced higher expression of MMP-3 mRNA and protein in synovial cells than direct stimulation by M. bovis. Recombinant bovine IL-1 beta also induced increased MMP-3 mRNA and protein expression in synovial cells. Our results indicate that M. bovis induces IL-1 beta expression by bovine mononuclear cells, and this cytokine then promotes MMP-3 production by synovial cells. These findings suggest that MMP-3 and IL-1 beta are key factors in the development of osteolysis in MA calves.