增生性瘢痕中的金黄色葡萄球菌“超载”通过TLR-2/AP-1/TGF-β1途径介导瘢痕成纤维细胞胶原产生的机制研究  

Mechanism research on staphylococcus aureus overload in hypertrophic scars mediates collagen production in scar fibroblasts through TLR-2/AP-1/TGF-β1 pathway

作　　者：余佳容 王西樵[1] Yu Jiarong;Wang Xiqiao(Department of Burn,Ruijin Hospital,Shanghai Jiao Tong University School of Medicine,Shanghai 200025,China)

机构地区：[1]上海交通大学医学院附属瑞金医院烧伤研究所,上海200025

出　　处：《感染、炎症、修复》2024年第4期255-261,共7页Infection Inflammation Repair

摘　　要：目的:探讨增生性瘢痕中的金黄色葡萄球菌“超载”对成纤维细胞纤维化功能的影响机制。方法:取16例行瘢痕切除和自体皮移植的增生性瘢痕住院患者的增生性瘢痕组织和正常皮肤组织进行固定切片。用革兰氏染色观察组织中的细菌,用免疫荧光检测是否为金黄色葡萄球菌,免疫组化和免疫印迹检测Toll样受体-2(TLR-2)、激活蛋白-1(AP-1)在组织中的表达。另外,选择灭活后的金黄色葡萄球菌干预正常成纤维细胞,观察细胞TLR-2、AP-1、转化生长因子-β1(TGF-β1)和胶原蛋白Ⅰ、Ⅲ表达变化的变化。最后,分别阻断TLR-2、AP-1的活性,观察TGF-β1和胶原蛋白Ⅰ、Ⅲ表达的变化。结果:革兰氏染色发现增生性瘢痕中革兰氏阳性细菌显著高于正常皮肤组织,免疫荧光检测为金黄色葡萄球菌。免疫组化和免疫印迹均提示瘢痕中TLR-2、AP-1表达显著高于正常皮肤。1×105CFU/mL金黄色葡萄球菌能显著促进正常成纤维细胞TLR-2、AP-1、TGF-β1和胶原蛋白Ⅰ、Ⅲ的表达。而用分别使用TLR-2和AP-1抑制剂处理细胞,发现均能显著抑制TGF-β1和胶原的产生。结论:增生性瘢痕的金黄色葡萄球菌“超载”,通过TLR-2/AP-1/TGF-β1途径促进胶原的产生,干预TLR-2或AP-1表达可能是未来瘢痕治疗手段之一。Objective:To investigate the mechanism underlying the influence of overloaded Staphylococcus aureus(S.aureus)on fibroblast collagen production in hypertrophic scars.Methods:The hypertrophic scar tissue and normal skin tissue of 16 inpatients with hypertrophic scar underwent scar resection and autologous skin transplantation were fixed sections.The bacteria in the tissues were observed by Gram staining,Staphylococcus aureus was detected by immunofluorescence,and the expression of toll-like receptor-2(TLR-2)and activator protein-1(AP-1)were detected by immunohistochemistry and western blot.Additionally,normal fibroblasts were cocultured with S.aureus at various concentrations,and the expression of TLR-2,AP-1,transforming growth factorβ1(TGF-β1),and collagen typesⅠandⅢwere analyzed.Furthermore,the effects of blocking TLR-2 or AP-1 on TGF-β1 and collagen production were evaluated.Results:Gram staining revealed a significantly higher number of positive bacteria in hypertrophic scar tissues compared to normal skin,and immunofluorescence confirmed the presence of S.aureus.Both immunohistochemistry and western blot indicated that the expression of TLR-2 and AP-1 in scar was significantly higher than that in normal skin.1×105CFU/mL S.aureus can significantly promote the expression of TLR-2,AP-1,TGF-β1,and collagenⅠandⅡin normal fibroblasts.While the cells were treated with TLR-2 and AP-1 inhibitors respectively,it was found that TGF-β1 and collagen production were significantly inhibited.Conclusions:Staphylococcus aureus in hypertrophic scars is"overloaded"and promotes collagen production through TLR-2/AP-1/TGF-β1 pathway.Intervention of TLR-2 or AP-1 expression represents a promising therapeutic approach for scar management.

关 键 词：增生性瘢痕 金黄色葡萄球菌 Toll样受体-2 激活蛋白-1 转化生长因子-β1 

分 类 号：R446.6[医药卫生—诊断学]