Propionibacterium acnes Induces Intervertebral Disc Degeneration by Promoting iNOS/NO and COX-2/PGE2 Activation via the ROS-Dependent NF-κB Pathway
Propionibacterium acnes Induces Intervertebral Disc Degeneration by Promoting iNOS/NO and COX-2/PGE2 Activation via the ROS-Dependent NF-κB Pathway
复制标题
痤疮丙酸杆菌通过 ROS 依赖性 NF-kappa B 途径促进 iNOS/NO 和 COX-2/PGE(2) 激活，从而诱导椎间盘退变
DOI：
10.1155/2018/3692752
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发表时间：
2018-01-01
影响因子：
--
通讯作者：
Cao, Peng
中科院分区：
文献类型：
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作者：
Lin, Yazhou;Tang, Guoqing;Cao, Peng
痤疮丙酸杆菌（Propionibacteriumacnes，P. acnes）是一种新的椎间盘退行性变的致病因子。然而，痤疮丙酸杆菌诱导IVDD的潜在机制尚不清楚。在本研究中，我们量化了IVDD的严重程度，以及诱导型一氧化氮合酶（iNOS）/一氧化氮（NO）和环氧合酶（考克斯-2）/前列腺素（PGE（2））在感染痤疮丙酸杆菌的人椎间盘（IVD）中的表达。与痤疮丙酸杆菌阴性的IVD相比，痤疮丙酸杆菌阳性的IVD显示iNOS/NO和考克斯-2/PGE（2）活性升高，并伴有更严重的IVD。为了检测iNOS/NO表达、考克斯-2/PGE（2）表达与IVDD之间的潜在相关性，我们建立了痤疮丙酸杆菌诱导的IVDD大鼠模型，发现iNOS/NO和考克斯-2/ PGE（2）的上调在痤疮丙酸杆菌诱导的IVDD的发生中是必要的。抑制iNOS/NO和考克斯-2/PGE（2）活性可显著改善IVDD，体内和体外聚集蛋白聚糖和II型胶原蛋白表达均恢复。从机制上讲，我们发现痤疮丙酸杆菌通过活性氧（ROS）依赖性NF-κ B级联反应诱导iNOS/NO和考克斯-2/PGE（2）表达。NADPH氧化酶参与痤疮丙酸杆菌诱导的ROS、iNOS/NO和考克斯-2/PGE（2）的表达。总之，这些发现进一步证实了痤疮丙酸杆菌参与了IVDD的病理过程，并提供了证据表明痤疮丙酸杆菌通过ROS依赖性NF-κ B途径诱导的iNOS/NO和考克斯-2/PGE（2）活化可能是IVDD病理过程的原因。
Accumulating evidence suggests that Propionibacterium acnes (P. acnes) is a novel pathogenic factor promoting intervertebral disc degeneration (IVDD). However, the underlying mechanisms by which P. acnes induces IVDD have been unclear. In this study, we quantified the severity of IVDD, as well as the expressions of inducible nitric oxide synthase (iNOS)/nitric oxide (NO) and cyclooxygenase (COX-2)/prostaglandin (PGE(2)) in human intervertebral discs (IVDs) infected with P. acnes. Compared with P. acnes-negative IVDs, P. acnes-positive IVDs showed increased iNOS/NO and COX-2/PGE(2) activity concomitant with more severe IVDD. In order to detect the potential correlation between iNOS/NO expression, COX-2/PGE(2) expression, and IVDD, we developed a P. acnes-induced IVDD rat model and found that the upregulation of iNOS/NO and COX-2/ PGE(2) was essential to the occurrence of P. acnes-induced IVDD. This finding was supported by the fact that the inhibition of iNOS/NO and COX-2/PGE(2) activity ameliorated IVDD significantly, as evidenced by restored aggrecan and collagen II expression both in vivo and in vitro. Mechanistically, we found that P. acnes induced iNOS/NO and COX-2/PGE(2) expressions via a reactive oxygen species-(ROS-) dependent NF-kappa B cascade. Furthermore, NADPH oxidase participated in P. acnes-induced ROS, iNOS/NO, and COX-2/PGE(2) expressions. Overall, these findings further validated the involvement of P. acnes in the pathology of IVDD and provided evidence that P. acnes-induced iNOS/NO and COX-2/PGE(2) activation via the ROS-dependent NF-kappa B pathway is likely responsible for the pathology of IVDD.