L-tryptophan in supraphysiologic concentrations stimulates collagenase gene expression in human skin fibroblasts

J. Varga*, L. Li, A. Mauviel, J. Jeffrey, S. A. Jimenez

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

17 Scopus citations

Abstract

BACKGROUND: Collagenase plays a critical role in regulating connective tissue breakdown in physiologic and pathologic processes. The expression of collagenase is modulated by a variety of biologic and pharmacologic agents. L-tryptophan is an essential amino acid with diverse biologic effects not shared by other amino acids. EXPERIMENTAL DESIGN: In this study, we examined the effects of L-tryptophan on collagenase gene expression in normal human skin fibroblasts using Northern hybridizations and transient transfection assays. RESULTS: The results indicate that L-tryptophan at supraphysiologic concentrations caused a marked increase in collagenase gene expression. The increase in collagenase mRNA levels was reversible, time- and dose-dependent, and was accompanied by enhancement of procollagenase synthesis and secretion. Parallel accumulation of mRNA for tissue inhibitor of metalloproteinase was also noted, whereas stromelysin mRNA levels remained undetectable. The enhancement of collagenase mRNA was specific for L-tryptophan, and was abrogated by α-amanitin or dexamethasone. The apparent half-life of collagenase mRNA transcripts was similar in cultures exposed to interleukin- 1β or L-tryptophan. In contrast to interleukin-1β, L-tryptophan-induced increase in collagenase mRNA was not preceeded by expression of c-jun or c- fos. Transient transfection of human skin fibroblasts with a collagenase promoter, chloramphenicol acetyl transferase construct indicated marked dose- dependent increase in promoter activity with L-tryptophan. CONCLUSIONS: These results demonstrate that L-tryptophan in supraphysiologic concentrations is a potent inducer of collagenase gene expression in vitro at a transcriptional level by human skin fibroblasts.

Original languageEnglish (US)
Pages (from-to)183-191
Number of pages9
JournalLaboratory Investigation
Volume70
Issue number2
StatePublished - 1994

Keywords

  • Amino acid
  • Fibroblasts
  • Metalloproteinase

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Molecular Biology
  • Cell Biology

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