Ketabchi S, Massi D, Ficarra G, Rubino I, Franchi A, Paglierani M, Simoni A, Capodiferro S, Favia G, Maiorano E, Tarantini F, Cirino G, Santucci M
Department of Human Pathology and Oncology, University of Florence, Florence, Italy.
Oral Dis. 2007 Jul;13(4):419-25. doi: 10.1111/j.1601-0825.2006.01317.x.
Orofacial granulomatosis (OFG) is a rare condition characterized by non-caseating granulomas in the orofacial region. Protease-Activated Receptors (PARs) play a role in inflammatory diseases in diverse human tissues. The aim of the study was to investigate the expression of PAR-1, PAR-2, MMP-2, MMP-9, COX-1, and COX-2 in tissues taken from OFG patients.
PAR-1, PAR-2, MMP-2, MMP-9, COX-1, and COX-2 expression was evaluated by immunohistochemistry in biopsies taken from oral Crohn's disease (five cases), Melkersson-Rosenthal syndrome (MRS) (six cases), cheilitis granulomatosa (five cases) and normal oral mucosa (five cases).
PAR-1 was observed in mononuclear inflammatory cells in edematous/lichenoid lesions, whereas a strong PAR-2 immunostaining was detected in epithelioid histiocytes and giant cells in granulomatous lesions, irrespective of the clinical features (Crohn vs MRS). MMPs and COX-2 were expressed in the inflammatory component of edematous/lichenoid lesions and markedly overexpressed in granulomatous lesions. COX-1 was weakly and variably expressed in both edematous/lichenoid and granulomatous lesions.
Thus, PAR-1 and PAR-2 expressions were related to the intensity and type of inflammatory response but not to the type of clinical lesion. Simultaneous overexpression of PARs, MMPs and COXs suggests synergism among these proinflammatory receptors and enzymes.
口面部肉芽肿病(OFG)是一种罕见疾病,其特征为口面部区域出现非干酪样肉芽肿。蛋白酶激活受体(PARs)在多种人体组织的炎症性疾病中发挥作用。本研究的目的是调查PAR-1、PAR-2、基质金属蛋白酶-2(MMP-2)、基质金属蛋白酶-9(MMP-9)、环氧化酶-1(COX-1)和环氧化酶-2(COX-2)在OFG患者组织中的表达情况。
采用免疫组织化学方法评估取自口腔克罗恩病(5例)、梅尔克森-罗森塔尔综合征(MRS)(6例)、肉芽肿性唇炎(5例)和正常口腔黏膜(5例)活检组织中PAR-1、PAR-2、MMP-2、MMP-9、COX-1和COX-2的表达。
在水肿/苔藓样病变的单核炎性细胞中观察到PAR-1,而在肉芽肿性病变的上皮样组织细胞和巨细胞中检测到强烈的PAR-2免疫染色,与临床特征无关(克罗恩病与MRS)。基质金属蛋白酶和COX-2在水肿/苔藓样病变的炎症成分中表达,并在肉芽肿性病变中明显过度表达。COX-1在水肿/苔藓样病变和肉芽肿性病变中均呈弱且可变的表达。
因此,PAR-1和PAR-2的表达与炎症反应的强度和类型有关,但与临床病变类型无关。PARs、基质金属蛋白酶和环氧化酶的同时过度表达提示这些促炎受体和酶之间存在协同作用。