结节病患者环孢素A介导的牙龈增生中组织蛋白酶B、D和L的调节

Cathepsin B, D, and L regulation in cyclosporin A-mediated gingival hyperplasia of a patient with sarcoidosis.

作者信息

Murai Osamu, Naruishi Koji, Ogihara Satoshi, Suwa Nagisa, Kanazawa Satomi, Yaegashi Takashi, Takeda Yasunori, Kunimatsu Kazushi

机构信息

Division of Periodontology, Department of Conservative Dentistry and Oral Rehabilitation, Japan.

出版信息

Clin Lab. 2011;57(7-8):535-41.

PMID:21888018

Abstract

BACKGROUND

Cyclosporin A (CsA) is an immunosuppressant with side effects including gingival hyperplasia. Sarcoidosis is a systemic disease characterized by granulomas. Here, we report on a rare case of sarcoidosis with gingival hyperplasia to clarify whether clinical observation corresponds to in vitro results.

METHODS

Gingival fibroblasts (HGFs) were isolated from healthy gingiva and cultured with CsA. Total RNA was collected and expression of mRNAs examined using semi-quantitative RT-PCR analysis. Cathepsin B, D, and L expression in overgrown gingiva of the patient was examined by immunohistochemistry.

RESULTS

Cathepsin D, L, and vascular endothelial growth factor (VEGF)165 mRNA were markedly suppressed in CsA-treated HGFs, whereas cathepsin B, matrix metalloproteinase-1 (MMP-1) and tissue inhibitor of metalloproteinase-1 (TIMP-1) mRNA were not reduced. Next, the decrease of cathepsin B and L expression in enlarged gingiva was observed, whereas an increase of cathepsin D expression was observed. Clinically, the enlarged gingival lesions were fully resolved by performing oral infection control.

CONCLUSIONS

Cathepsins regulation might be an important factor in the development of CsA-mediated gingival hyperplasia.

摘要

背景

环孢素A（CsA）是一种免疫抑制剂，其副作用包括牙龈增生。结节病是一种以肉芽肿为特征的全身性疾病。在此，我们报告一例罕见的结节病合并牙龈增生病例，以阐明临床观察结果是否与体外实验结果相符。

方法

从健康牙龈中分离牙龈成纤维细胞（HGFs），并用CsA进行培养。收集总RNA，采用半定量逆转录-聚合酶链反应（RT-PCR）分析检测mRNA的表达。通过免疫组织化学检测患者增生牙龈中组织蛋白酶B、D和L的表达。

结果

在经CsA处理的HGFs中，组织蛋白酶D、L和血管内皮生长因子（VEGF）165 mRNA明显受到抑制，而组织蛋白酶B、基质金属蛋白酶-1（MMP-1）和金属蛋白酶组织抑制剂-1（TIMP-1）mRNA未降低。接下来，观察到增生牙龈中组织蛋白酶B和L的表达降低，而组织蛋白酶D的表达增加。临床上，通过进行口腔感染控制，增生的牙龈病变完全消退。