Teymoortash Afshin, Mandic Robert, Schrader Carsten, Werner Jochen Alfred
Department of Otolaryngology, Head and Neck Surgery, Philipps University, Marburg, Germany.
J Oral Sci. 2004 Dec;46(4):227-33. doi: 10.2334/josnusd.46.227.
The exact pathomechanism of inflammation progress and fibrosis in chronic sialadenitis is unknown. Connective tissue growth factor (CTGF), matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) have been implicated in the pathogenesis of various fibrotic conditions. These factors are thought to be essential in the regulation of extracellular matrix turnover and the development of tissue fibrosis. In the present study, the expression of CTGF, MMP-2, -3, -9, -13 and TIMP-3 was examined in chronic obstructive sialadenitis. Tissue samples of 13 patients with chronic sialadenitis of the submandibular gland associated with sialolithiasis and 4 normal tissue samples of the submandibular gland were analyzed immunohistochemically and by Western blot analysis. An intense CTGF immunoreactivity was observed in the ductal system of inflamed salivary glands, whereas in normal glands no reactivity or a very low CTGF immunoreactivity was present. Immunohistochemical studies revealed a low to strong reactivity of MMP-2, -3, -9, -13, and TIMP-3 in the ductal system, in acinar cells and in lymphomonocytic infiltrates in normal and inflamed tissues. The expression of MMP-2, -3, -9, -13, and TIMP-3 was confirmed by Western blotting in all cases. Over-expression of CTGF in chronic obstructive sialadenitis suggests that this factor may play a role in glandular fibrosis. However, the physiological role of MMP-2, -3, -9, -13, and TIMP-3 in normal glands, as well as their possible role in inflammation progress and fibrosis in chronic obstructive sialadenitis, remains to be elucidated.
慢性涎腺炎中炎症进展和纤维化的确切发病机制尚不清楚。结缔组织生长因子（CTGF）、基质金属蛋白酶（MMPs）和金属蛋白酶组织抑制剂（TIMPs）与各种纤维化疾病的发病机制有关。这些因子被认为在细胞外基质周转调节和组织纤维化发展中至关重要。在本研究中，检测了慢性阻塞性涎腺炎中CTGF、MMP-2、-3、-9、-13和TIMP-3的表达。对13例伴有涎石病的下颌下腺慢性涎腺炎患者的组织样本和4例正常下颌下腺组织样本进行了免疫组织化学和蛋白质印迹分析。在炎症唾液腺的导管系统中观察到强烈的CTGF免疫反应性，而在正常腺体中没有反应或只有非常低的CTGF免疫反应性。免疫组织化学研究显示，在正常和炎症组织的导管系统、腺泡细胞和淋巴细胞浸润中，MMP-2、-3、-9、-13和TIMP-3有低至强的反应性。在所有病例中，蛋白质印迹法证实了MMP-2、-3、-9、-13和TIMP-3的表达。慢性阻塞性涎腺炎中CTGF的过度表达表明该因子可能在腺体纤维化中起作用。然而，MMP-2、-3、-9、-13和TIMP-3在正常腺体中的生理作用，以及它们在慢性阻塞性涎腺炎炎症进展和纤维化中的可能作用，仍有待阐明。
