Suzuki S, Tourkina E, Ludwicka A, Hampton M, Bolster M, Maize J, Silver R
Department of Medicine, Medical University of South Carolina, Charleston, 29425-2229, USA.
Proc Assoc Am Physicians. 1996 Jul;108(4):315-22.
The eosinophilia-myalgia syndrome was associated with the ingestion of L-tryptophan products containing a number of contaminants, one of which has been identified as 1,1'-ethylidene-bis-(L-tryptophan) (EBT), also known as peak E or peak 97. In earlier studies, we demonstrated that EBT induces inflammation and fibrosis in dermal and subcutaneous tissue of C57BL/6 mice. Others have shown EBT to be a potent stimulus for fibroblast activation and collagen synthesis in vitro, and dermal tissue from EMS patients reveals evidence of enhanced collagen gene expression. In the present study using Northern blot analysis and in situ hybridization, we demonstrate enhanced expression of genes for types I, III, and VI collagen in the dermis and subcutis of C57BL/6 mice treated with EBT for 3-21 days. Increased type I procollagen mRNA was noted on day 6 of EBT treatment and was followed by enhanced expression of type III and VI procollagen mRNA at day 21. L-Tryptophan, free of contaminants associated with the eosinophilia-myalgia syndrome epidemic, increased dermal collagen mRNA to a lesser extent than did EBT. Increased procollagen gene expression was accompanied by evidence of enhanced TGF-beta 1 expression in the dermis and subcutis. This animal model provides additional evidence for EBT as a causal agent of the eosinophilia-myalgia syndrome and should prove useful in the study of the pathogenesis of that syndrome.
嗜酸性粒细胞增多性肌痛综合征与摄入含有多种污染物的L-色氨酸产品有关，其中一种污染物已被鉴定为1,1'-亚乙基-双-(L-色氨酸)(EBT)，也称为峰E或峰97。在早期研究中，我们证明EBT可诱导C57BL/6小鼠皮肤和皮下组织发生炎症和纤维化。其他人已表明EBT在体外是成纤维细胞活化和胶原蛋白合成的有效刺激物，并且嗜酸性粒细胞增多性肌痛综合征患者的皮肤组织显示出胶原蛋白基因表达增强的证据。在本研究中，使用Northern印迹分析和原位杂交，我们证明在用EBT处理3至21天的C57BL/6小鼠的真皮和皮下组织中，I型、III型和VI型胶原蛋白基因的表达增强。在EBT处理的第6天观察到I型前胶原mRNA增加，随后在第21天III型和VI型前胶原mRNA的表达增强。不含与嗜酸性粒细胞增多性肌痛综合征流行相关污染物的L-色氨酸，其增加皮肤胶原蛋白mRNA的程度小于EBT。前胶原基因表达增加伴随着真皮和皮下组织中TGF-β1表达增强的证据。这个动物模型为EBT作为嗜酸性粒细胞增多性肌痛综合征的病因提供了额外的证据，并且应该在该综合征的发病机制研究中证明是有用的。
