A contaminant of L-tryptophan enhances expression of dermal collagen in a murine model of eosinophilia myalgia syndrome.
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.
Suzuki
S
S
Department of Medicine, Medical University of South Carolina, Charleston, 29425-2229, USA.
Tourkina
E
E
Ludwicka
A
A
Hampton
M
M
Bolster
M
M
Maize
J
J
Silver
R
R
D000818:Animals; D015152:Blotting, Northern; D003094:Collagen / Q000235:genetics / Q000378:metabolism*; D004195:Disease Models, Animal; D016603:Eosinophilia-Myalgia Syndrome / Q000378:metabolism* / Q000473:pathology; D005260:Female; D017403:In Situ Hybridization; D051379:Mice; D008810:Mice, Inbred C57BL; D012333:RNA, Messenger; D014364:Tryptophan / Q000008:administration & dosage / Q000031:analogs & derivatives*
D012333:RNA, Messenger; C070372:1,1'-ethylidene bis(tryptophan); D014364:Tryptophan; D003094:Collagen