Department of Oral Medicine, Shanghai Ninth People's Hospital, College of Stomatology, Shanghai Jiao Tong University School of Medicine, National Clinical Research Center for Oral Diseases, Shanghai Key Laboratory of Stomatology & Shanghai Research Institute of Stomatology, Shanghai, China.
Shanghai Institute of Immunology, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
J Oral Pathol Med. 2020 Apr;49(4):350-356. doi: 10.1111/jop.12938. Epub 2019 Aug 19.
To explore the expression and functions of the tripartite motif-containing protein 21 (TRIM21) in oral lichen planus(OLP) lesions.
Paraffin sections of buccal mucosa samples from 15 cases of reticular oral lichen planus (OLP) patients and 10 healthy controls were used for immunohistochemistry to determine expression and distribution of TRIM21. Buccal mucosae from 11 OLP patients and seven healthy controls were analyzed by qPCR to quantify its gene expression. Peripheral blood mononuclear cells and CD3+ cells from four pairs of age- and sex-matched OLP patients and healthy controls were isolated for immunocytochemistry and culture. Following lentivirus-mediated overexpression of TRIM21 gene in CD3+ cells, CCK-8 was applied to evaluate cell proliferation. Cytokines including IL-2, IL-4, IL-5, IL-6, IL-10, TNF-α, and IFN-γ in the supernatants were measured by the cytometric bead array and verified by ELISA.
A larger number of TRIM21-positive cells infiltrating the lamina propria were observed in OLP lesions by immunohistochemistry than those of healthy controls. Significantly higher transcription of TRIM21 was revealed by qPCR. TRIM21 overexpression in CD3+ cells significantly enhanced the proliferation and IL-6 secretion in CD3+ cells from 12 to 72 hours.
Overexpressed TRIM21 in OLP may be a primary proinflammatory molecule rather than a secondary and inducible regulatory factor in immunopathogenesis of OLP.
探讨三结构域蛋白 21(TRIM21)在口腔扁平苔藓(OLP)病变中的表达和功能。
采用免疫组织化学法检测 15 例网状型口腔扁平苔藓(OLP)患者和 10 例健康对照者颊黏膜石蜡切片中 TRIM21 的表达和分布。采用 qPCR 分析 11 例 OLP 患者和 7 例健康对照者颊黏膜组织中其基因表达。采用免疫细胞化学和培养法分离 4 对年龄和性别匹配的 OLP 患者和健康对照者的外周血单个核细胞和 CD3+细胞。采用慢病毒介导的 TRIM21 基因过表达后,用 CCK-8 法评估细胞增殖。采用细胞因子微珠阵列法和 ELISA 法检测上清液中包括 IL-2、IL-4、IL-5、IL-6、IL-10、TNF-α和 IFN-γ在内的细胞因子。
免疫组织化学显示,OLP 病变中固有层浸润的 TRIM21 阳性细胞较健康对照组增多。qPCR 显示 TRIM21 转录水平明显升高。TRIM21 在 CD3+细胞中的过表达显著增强了 CD3+细胞的增殖和 12 至 72 小时的 IL-6 分泌。
OLP 中过表达的 TRIM21 可能是 OLP 免疫发病机制中的主要促炎分子,而不是二级和诱导性调节因子。