Various secretory phospholipase A2 enzymes are expressed in rheumatoid arthritis and augment prostaglandin production in cultured synovial cells
Various secretory phospholipase A2 enzymes are expressed in rheumatoid arthritis and augment prostaglandin production in cultured synovial cells
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DOI：
10.1111/j.1742-4658.2004.04489.x
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发表时间：
2005-02-01
期刊：
影响因子：
5.4
通讯作者：
Kudo, I
中科院分区：
文献类型：
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作者：
Masuda, S;Murakami, M;Kudo, I
尽管已知类风湿性关节炎 (RA) 患者的关节中大量存在 IIA 族分泌性磷脂酶 A(2) (sPLA(2)-IIA)，但该疾病中其他 sPLA(2)S 的表达仍不清楚。在这项研究中，我们检测了人类 RA 中六种 sPLA(2)S（IIA、IID、IIE、IIF、V 和 X 组）的表达和定位。 RA切片的免疫组织化学显示，sPLA（2）-IIA通常位于滑膜衬层和亚衬细胞以及软骨细胞中，sPLA（2）-IID位于淋巴滤泡和毛细血管内皮细胞中，sPLA（2）-IIE位于血管平滑肌细胞中，sPLA（2）-V位于间质成纤维细胞中。这些 II 组亚家族 sPLA(2) 的表达水平在严重 RA 中似乎比非活动性 RA 中更高。在活动性和非活动性 RA 切片的滑膜衬里细胞和间质纤维中均检测到 sPLA(2)-X。 sPLA(2)-IIF的表达部分呈阳性，但其与疾病状态的相关性尚不清楚。 sPLA(2) 转录物的表达在培养的正常人滑膜细胞中也很明显，其中sPLA(2)-IIA 和-V 由白细胞介素-1 诱导，sPLA(2)-X 组成型表达。腺病毒介导的sPLA(2)S在培养的滑膜细胞中的表达导致在低ng.mL(-1)浓度下前列腺素E-2的产生增加。因此，多种 sPLA(2) 在人类 RA 中表达，它们可能在增强花生四烯酸代谢中发挥作用或表现出其他细胞类型特异性功能。
Although group IIA secretory phospholipase A(2) (sPLA(2)-IIA) is known to be abundantly present in the joints of patients with rheumatoid arthritis (RA), expression of other sPLA(2)S in this disease has remained unknown. In this study, we examined the expression and localization of six sPLA(2)S (groups IIA, IID, IIE, IIF, V and X) in human RA. Immunohistochemistry of RA sections revealed that sPLA(2)-IIA was generally located in synovial lining and sublining cells and cartilage chondrocytes, sPLA(2)-IID in lymph follicles and capillary endothelium, sPLA(2)-IIE in vascular smooth muscle cells, and sPLA(2)-V in interstitial fibroblasts. Expression levels of these group II subfamily sPLA(2)s appeared to be higher in severe RA than in inactive RA. sPLA(2)-X was detected in synovial lining cells and interstitial fibers in both active and inactive RA sections. Expression of sPLA(2)-IIF was partially positive, yet its correlation with disease states was unclear. Expression of sPLA(2) transcripts was also evident in cultured normal human synoviocytes, in which sPLA(2)-IIA and -V were induced by interleukin-1 and sPLA(2)-X was expressed constitutively. Adenovirus-mediated expression of sPLA(2)S in cultured synoviocytes resulted in increased prostaglandin E-2 production at low ng.mL(-1) concentrations. Thus, multiple sPLA(2)s are expressed in human RA, in which they may play a role in the augmentation of arachidonate metabolism or exhibit other cell type-specific functions.