Increased type I collagen gene expression in L-tryptophan associated eosinophilia-myalgia syndrome skin fibroblasts.
OBJECTIVE
To investigate the pathogenetic mechanisms responsible for the cutaneous fibrosis in eosinophilia-myalgia syndrome (EMS) associated with L-tryptophan ingestion.


METHODS
Compare in vitro type I collagen production and steady state procollagen mRNA levels in cultured skin fibroblasts derived from healthy individuals and from 5 patients with EMS and diffuse cutaneous induration.


RESULTS
Cell lines derived from the affected skin from patients with EMS exhibited greater collagen production and higher steady state levels of alpha 1(I) procollagen mRNA compared with fibroblasts from age and sex matched healthy individuals. Exposure to interferon gamma reduced collagen synthesis in the EMS fibroblast lines. The rate of in vitro transcription of the COL1A1 gene was 30% higher in nuclei isolated from collagen overproducer EMS fibroblasts than in nuclei from normal fibroblasts.


CONCLUSIONS
Fibroblasts derived from the involved skin of patients with EMS show increased expression of the alpha 1(I) procollagen gene in vitro compared to normal skin fibroblasts. The biosynthetically activated phenotype exhibited by EMS fibroblasts appears to be due, at least in part, to transcriptional activation of type I collagen gene expression. These biochemical and molecular alterations may result in accumulation of collagen and lead to the cutaneous fibrosis in EMS.
Varga
J
J
Department of Medicine, Jefferson Medical College, Thomas Jefferson University, Philadelphia, PA 19107.
Li
L
L
Jimenez
S A
SA
D000328:Adult; D002478:Cells, Cultured; D003094:Collagen / Q000235:genetics / Q000378:metabolism*; D016603:Eosinophilia-Myalgia Syndrome / Q000139:chemically induced / Q000235:genetics* / Q000473:pathology; D005260:Female; D005347:Fibroblasts / Q000378:metabolism / Q000502:physiology; D015870:Gene Expression; D006706:Homeostasis; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology; D008297:Male; D008875:Middle Aged; D011347:Procollagen / Q000235:genetics; D012333:RNA, Messenger / Q000378:metabolism; D012867:Skin / Q000473:pathology / Q000503:physiopathology*; D014364:Tryptophan / Q000009:adverse effects
D011347:Procollagen; D012333:RNA, Messenger; D007371:Interferon-gamma; D014364:Tryptophan; D003094:Collagen