1,1'-Ethylidenebis[L-tryptophan], an impurity in L-tryptophan associated with eosinophilia-myalgia syndrome, stimulates type I collagen gene expression in human fibroblasts in vitro.
Eosinophilia-myalgia syndrome (EMS), a recently described inflammatory disorder characterized by myalgia, peripheral eosinophilia, and multisystem inflammation is associated with L-tryptophan consumption. Fibrosis of various tissues due to excessive accumulation of type I collagen is a prominent late manifestation of the syndrome. 1,1'-Ethylidenebis[L-tryptophan] (EBT), an impurity distinct from L-tryptophan found in case-associated lots, has been implicated in function in vitro. Incubation of confluent fibroblasts with EBT, but not its hydrolysis product 1-methyl-tetrahydro-beta-carboline-3-carboxylic acid, caused a dose-dependent increase in collagen synthesis and in type I collagen mRNA levels independent of its effect on proliferation. In contrast, expression mRNA for fibronectin was not affected. These findings indicate that EBT stimulates type I collagen production by human fibroblast, and suggest that EBT may be involved in the development of fibrosis in EMS.
Zangrilli
J G
JG
Division of Pulmonary/Critical Care, Jefferson Medical College, Philadelphia, PA, USA.
Mayeno
A N
AN
Vining
V
V
Varga
J
J
D002243:Carbolines / Q000494:pharmacology; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D003094:Collagen / Q000096:biosynthesis / Q000235:genetics*; D016603:Eosinophilia-Myalgia Syndrome / Q000139:chemically induced*; D005109:Extracellular Matrix / Q000378:metabolism; D005347:Fibroblasts / Q000187:drug effects; D005786:Gene Expression Regulation / Q000187:drug effects*; D006801:Humans; D013268:Stimulation, Chemical; D014364:Tryptophan / Q000009:adverse effects* / Q000031:analogs & derivatives* / Q000302:isolation & purification
D002243:Carbolines; C070372:1,1'-ethylidene bis(tryptophan); C038114:1-methyl-1,2,3,4-tetrahydro-beta-carboline-3-carboxylic acid; D014364:Tryptophan; D003094:Collagen