Key Laboratory for Oral Biomedical Engineering of Ministry of Education, School & Hospital of Stomatology, Wuhan University, 237 Luo Yu Road, Hongshan District, Wuhan 430079, China.
Biochem Biophys Res Commun. 2010 Jan 1;391(1):1000-6. doi: 10.1016/j.bbrc.2009.12.005. Epub 2009 Dec 5.
CypA is able to regulate inflammatory responses and MMPs production via interaction with its cell surface receptor, EMMPRIN. This study aimed to address the possible association of CypA with pathological inflammation and destruction of periodontal tissues, and whether CypA-EMMPRIN interaction exists in periodontitis.
Experimental periodontitis was induced by ligation according to our previous method. Histological and radiographic examinations were performed. Western blot was used to detect CypA and EMMPRIN expressions in gingival tissues. Immunohistochemistry was applied for CypA, EMMPRIN, MMP-1, MMP-2, MMP-9, as well as cell markers of macrophage, lymphocyte and neutrophil. CypA expression, alveolar bone loss, and inflammatory infiltrations were quantified followed by correlation analyses.
Western blot revealed that CypA and EMMRPIN expressions were dramatically elevated in inflamed gingival tissues (ligature group) as compared to healthy gingival tissues (control group). The enhanced CypA and EMMPRIN expressions were highly consistent in cell localization on seriate sections. They were permanently co-localized in infiltrating macrophages and lymphocytes, as well as osteoclasts and osteoblasts in interradicular bone, but rarely expressed by infiltrating neutrophils. MMP-1, MMP-2, and MMP-9 expressions were also sharply increased in inflamed gingiva. MMP-2 and MMP-9 were mainly over-expressed by macrophages, while MMP-1 was over-produced by fibroblasts and infiltrating cells. The number of CypA-positive cells was strongly correlated with the ACJ-AC distance (r=0.839, p=0.000), the number of macrophages (r=0.972, p=0.000), and the number of lymphocytes (r=0.951, p=0.000).
CypA is associated with the inflammatory infiltration and alveolar bone destruction of periodontitis. CypA-EMMPRIN interaction may exist in these pathological processes.
亲环素 A(CypA)能够通过与其细胞表面受体细胞外基质金属蛋白酶诱导因子(EMMPRIN)相互作用来调节炎症反应和 MMPs 的产生。本研究旨在探讨 CypA 是否与牙周组织的病理性炎症和破坏有关,以及 CypA-EMMPRIN 相互作用是否存在于牙周炎中。
根据我们之前的方法,通过结扎诱导实验性牙周炎。进行组织学和影像学检查。使用 Western blot 检测牙龈组织中 CypA 和 EMMPRIN 的表达。应用免疫组织化学检测 CypA、EMMPRIN、MMP-1、MMP-2、MMP-9 以及巨噬细胞、淋巴细胞和中性粒细胞的细胞标志物。对 CypA 表达、牙槽骨丧失和炎症浸润进行定量分析,并进行相关性分析。
Western blot 显示,与健康牙龈组织(对照组)相比,炎症性牙龈组织(结扎组)中 CypA 和 EMMPRIN 的表达显著增加。在连续切片上,增强的 CypA 和 EMMPRIN 表达在细胞定位上高度一致。它们在浸润的巨噬细胞和淋巴细胞中,以及在根尖骨中的破骨细胞和成骨细胞中永久共定位,但很少在浸润的中性粒细胞中表达。MMP-1、MMP-2 和 MMP-9 的表达也在炎症性牙龈中明显增加。MMP-2 和 MMP-9 主要由巨噬细胞过度表达,而 MMP-1 则由成纤维细胞和浸润细胞过度产生。CypA 阳性细胞的数量与 ACJ-AC 距离(r=0.839,p=0.000)、巨噬细胞数量(r=0.972,p=0.000)和淋巴细胞数量(r=0.951,p=0.000)呈强相关。
CypA 与牙周炎的炎症浸润和牙槽骨破坏有关。CypA-EMMPRIN 相互作用可能存在于这些病理过程中。