Increased activity of the alpha 1(I) procollagen promoter in skin fibroblasts from patients with chronic eosinophilia-myalgia syndrome.
Eosinophilia-myalgia syndrome (EMS), a novel L-tryptophan-associated disease, which occurred as an epidemic in 1989, is characterized by diffuse fibrosis of the skin. The objective of these studies was to compare the in vitro expression of the gene encoding the human alpha 1(I) procollagen (COL1A1) in dermal fibroblasts derived from patients with long-standing EMS and from healthy controls. Early passage fibroblasts in culture were transiently transfected with a series of progressively 5' deleted human COL1A1 promoter-CAT reporter gene DNA constructs. Resultant CAT activity was assayed in the cytoplasmic extracts. Following transient transfection, COL1A1 promoter activity in 4/5 fibroblast cell lines derived from patients with EMS was two-to threefold greater than in matched normal fibroblasts. Deletion analysis indicated that CAT activity was highest, and displayed the greatest increase in EMS vs normal fibroblasts, with promoter constructs spanning 174 bp upstream from the COL1A1 transcription start site. The study shows increased CAT activity driven by a 174 bp fragment of COL1A1 in transiently transfected skin fibroblasts from patients with EMS even in the chronic stage of disease. These findings expand on previous observations indicating increased type I collagen gene expression in EMS fibroblasts, and suggest that fibrosis in L-tryptophan-induced EMS is associated with transcriptional activation of type I collagen gene expression, which persists even following cessation of L-tryptophan use.
Hitraya
E G
EG
Division of Rheumatology, Jefferson Medical College, Thomas Jefferson University, Philadelphia, USA.
Jimenez
S A
SA
Ludwicka
A
A
Silver
R M
RM
Varga
J
J
D000328:Adult; D002460:Cell Line; D015500:Chloramphenicol O-Acetyltransferase / Q000235:genetics; D004340:Drug Contamination; D016603:Eosinophilia-Myalgia Syndrome / Q000139:chemically induced / Q000235:genetics*; D005260:Female; D005347:Fibroblasts / Q000378:metabolism; D015870:Gene Expression; D017930:Genes, Reporter; D006801:Humans; D008875:Middle Aged; D011347:Procollagen / Q000235:genetics*; D011401:Promoter Regions, Genetic; D012867:Skin / Q000378:metabolism; D014162:Transfection; D014364:Tryptophan / Q000506:poisoning
D011347:Procollagen; D014364:Tryptophan; D015500:Chloramphenicol O-Acetyltransferase