Beauséjour A, Grenier D, Goulet J P, Deslauriers N
Groupe de Recherche en Ecologie Buccale, Faculté de Médecine Dentaire et Faculté des Sciences et de Génie, Université Laval, Québec, Canada.
Infect Immun. 1998 Feb;66(2):676-81. doi: 10.1128/IAI.66.2.676-681.1998.
Chronic inflammation rather than invasion is characteristic of some forms of superficial candidiasis such as denture stomatitis. We hypothesized that Candida albicans may play a critical role in the pathogenesis of inflammatory lesions observed in chronic candidiasis by activating the proinflammatory cytokine interleukin-1beta (IL-1beta) from epithelial stores of the precursor. The aim of this study was therefore to demonstrate the proteolytic cleavage and activation of the inactive precursor of IL-1beta (pro-IL-1beta) by C. albicans. After incubation of either blastospores or hyphae with the inactive precursor, proteolytic cleavage was monitored by sodium dodecyl sulfate-polyacrylamide gel electrophoresis Western immunoblotting analysis, and the biological activity of the cleavage products was tested in a bioassay. We report here that late-stationary-growth-phase blastospores as well as hyphae of C. albicans, but not exponentially growing cells, can efficiently cleave pro-IL-1beta to yield fragments of molecular masses compatible with mature biologically active IL-1beta (17 to 19 kDa). Assays conducted in the presence of selected proteinase inhibitors suggest that the cleavage of pro-IL-1beta involves the participation of one or more aspartyl proteinases. Cleavage products showed a dose-dependent IL-1beta-like activity in a thymocyte proliferation bioassay, which was inhibited by anti-IL-1beta neutralizing antibodies. The present data thus suggest a role for C. albicans proteinases in the activation and maintenance of the inflammatory response at epithelial surfaces.
某些形式的浅表念珠菌病（如义齿性口炎）的特征是慢性炎症而非侵袭。我们推测白色念珠菌可能通过激活前体上皮储存中的促炎细胞因子白细胞介素 -1β（IL -1β），在慢性念珠菌病中观察到的炎症病变发病机制中发挥关键作用。因此，本研究的目的是证明白色念珠菌对IL -1β无活性前体（pro -IL -1β）的蛋白水解切割和激活作用。将芽生孢子或菌丝与无活性前体孵育后，通过十二烷基硫酸钠 - 聚丙烯酰胺凝胶电泳免疫印迹分析监测蛋白水解切割情况，并在生物测定中测试切割产物的生物活性。我们在此报告，白色念珠菌的稳定期后期芽生孢子以及菌丝，而非指数生长期的细胞，能够有效地切割pro -IL -1β，产生与成熟生物活性IL -1β（17至19 kDa）分子量相符的片段。在选定蛋白酶抑制剂存在下进行的测定表明，pro -IL -1β的切割涉及一种或多种天冬氨酸蛋白酶的参与。在胸腺细胞增殖生物测定中，切割产物显示出剂量依赖性的IL -1β样活性，该活性被抗IL -1β中和抗体抑制。因此，目前的数据表明白色念珠菌蛋白酶在上皮表面炎症反应的激活和维持中发挥作用。
