Leukoregulin down-regulates type I collagen mRNA levels and promoter activity in human dermal fibroblasts, and counteracts the up-regulation elicited by transforming growth factor-beta.
Leukoregulin (LR), a T-cell-derived growth factor, modulates fibroblast functions in vitro [Mauviel, Rédini, Hartmann, Loyau & Pujol (1991) J. Cell Biol. 113, 1455-1462]. In the present study, incubation of human dermal fibroblasts with LR (0.1-2 units/ml) resulted in decreases in the mRNA steady-state levels for alpha 1(I), alpha 2(I) and alpha 1(III), but not alpha 2(V), collagen genes. LR also down-regulated alpha 2(I) collagen promoter activity in transient cell transfections of control cells as well as those incubated with transforming growth factor-beta, a potent up-regulator of collagen type I gene expression. Thus LR is a strong inhibitor of type I collagen gene expression, acting at the level of transcription.
Mauviel
A
A
Department of Dermatology, Jefferson Medical College, Philadelphia, PA.
Evans
C H
CH
Uitto
J
J
D000970:Antineoplastic Agents / Q000494:pharmacology*; D002478:Cells, Cultured; D003094:Collagen / Q000235:genetics*; D005347:Fibroblasts / Q000187:drug effects / Q000502:physiology; D005786:Gene Expression Regulation / Q000187:drug effects*; D006801:Humans; D007700:Kinetics; D008222:Lymphokines / Q000494:pharmacology*; D011401:Promoter Regions, Genetic / Q000187:drug effects*; D012333:RNA, Messenger / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D012867:Skin / Q000187:drug effects; D012879:Skin Physiological Phenomena; D016212:Transforming Growth Factor beta / Q000037:antagonists & inhibitors / Q000494:pharmacology*
D000970:Antineoplastic Agents; D008222:Lymphokines; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta; C044162:leukoregulin; D003094:Collagen