Ogura N, Shibata Y, Matsuda U, Oikawa T, Takiguchi H, Izumi H, Abiko Y
Department of Oral Surgery, Nihon University School of Dentistry, Chiba, Japan.
J Periodontal Res. 1995 Mar;30(2):132-40. doi: 10.1111/j.1600-0765.1995.tb01262.x.
The plasminogen activator (PA)-plasmin system is implicated in the degradation of the extracellular matrix in inflammation through activation of metalloproteases and prekallikrein. We examined the activation of the PA-plasmin system in human gingival fibroblast cells (Gin-1 cells) following treatment with lipopolysaccharide (LPS) from Campylobacter rectus, which is frequently detected at sites of periodontal disease. The C. rectus LPS stimulated the plasmin activity in the conditioned medium of Gin-1 cells in a time- and dose-dependent manner, and C. rectus LPS also stimulated the PA activity in the conditioned medium. The PA produced by Gin-1 cells was determined to be urokinase PA (uPA), as preincubation of Gin-1 conditioned medium with anti-uPA antiserum completely inhibited the PA activity while that with anti-tPA antiserum had no inhibitory effect. The concentration of PA inhibitor-1 (PAI-1) in the conditioned medium was decreased by the addition of C. rectus LPS. Therefore, the enhancement of plasmin activity in the conditioned medium was dependent on increased uPA activity via the decrease of the PAI-1 level of Gin-1 cells treated with C. rectus LPS. Furthermore, the conditioned medium of Gin-1 cells treated with C. rectus LPS showed significantly increased kallikrein activity, indicating the conversion of prekallikrein to kallikrein, which converts kininogen into kinin. These findings suggest that C. rectus LPS is a potent stimulator of inflammation of gingival tissue which acts through stimulation of the PA-plasmin system.
纤溶酶原激活物（PA）-纤溶酶系统通过激活金属蛋白酶和前激肽释放酶参与炎症过程中细胞外基质的降解。我们检测了用直形弯曲杆菌的脂多糖（LPS）处理后人牙龈成纤维细胞（Gin-1细胞）中PA-纤溶酶系统的激活情况，直形弯曲杆菌在牙周病部位经常被检测到。直形弯曲杆菌LPS以时间和剂量依赖的方式刺激Gin-1细胞条件培养基中的纤溶酶活性，并且直形弯曲杆菌LPS也刺激条件培养基中的PA活性。经测定，Gin-1细胞产生的PA为尿激酶型PA（uPA），因为将Gin-1条件培养基与抗uPA抗血清预孵育可完全抑制PA活性，而与抗tPA抗血清预孵育则无抑制作用。添加直形弯曲杆菌LPS可降低条件培养基中PA抑制剂-1（PAI-1）的浓度。因此，条件培养基中纤溶酶活性的增强依赖于经直形弯曲杆菌LPS处理的Gin-1细胞PAI-1水平降低导致的uPA活性增加。此外，经直形弯曲杆菌LPS处理的Gin-1细胞的条件培养基显示激肽释放酶活性显著增加，表明前激肽释放酶转化为激肽释放酶，后者将激肽原转化为激肽。这些发现表明直形弯曲杆菌LPS是牙龈组织炎症的有效刺激物，其通过刺激PA-纤溶酶系统发挥作用。
