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 d isease, which occurred as an epidemic in 1989, is characterized by dif fuse fibrosis of the skin. The objective of these studies was to compa re the in vitro expression of the gene encoding the human alpha 1(I) p rocollagen (COL1A1) in dermal fibroblasts derived from patients with l ong-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. Re sultant CAT activity was assayed in the cytoplasmic extracts. Followin g transient transfection, COL1A1 promoter activity in 4/5 fibroblast c ell 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 v s normal fibroblasts, with promoter constructs spanning 174 hp upstrea m from the COL1A1 transcription start site. The study shows increased CAT activity driven by a 174 bp fragment of COL1A1 in transiently tran sfected skin fibroblasts from patients with EMS even in the chronic st age of disease. These findings expand on previous observations indicat ing increased type I collagen gene expression in EMS fibroblasts, and suggest that fibrosis in L-tryptophan-induced EMS is associated with t ranscriptional activation of type I collagen gene expression, which pe rsists even following cessation of L-tryptophan use. (C) 1997 Elsevier Science Ltd.