Role of serum amyloid A as an intermediate in the IL-1 and PMA-stimulated signaling pathways regulating expression of rabbit fibroblast collagenase

Exp Cell Res. 1997 Dec 15;237(2):275-87. doi: 10.1006/excr.1997.3783.


The matrix metalloproteinase collagenase is expressed by resident tissue cells only when needed for biological remodeling. Exogenous addition of inflammatory and growth-promoting cytokines stimulates collagenase expression in early passage fibroblast cultures. In addition, the signal for collagenase expression in response to phorbol-12 myristate-13 acetate (PMA) or to agents which alter cell shape in early passage fibroblast cultures is routed extracellularly to an autocrine cytokine intermediate, IL-1 alpha. Importantly, fibroblasts, when freshly isolated from the tissue, are not competent for IL-1 alpha gene expression and, therefore, cannot produce collagenase in response to shape change agents. However, they do make a small amount of collagenase in response to PMA via an IL-1-independent pathway that has not been further characterized. In this paper, we investigate the role of a second autocrine, serum amyloid A3 (SAA3), in IL-1-dependent and -independent collagenase gene expression. We demonstrate that SAA3 is required for effective stimulation of collagenase expression by either exogenous or endogenous IL-1. Furthermore, while freshly isolated fibroblasts cannot express IL-1 alpha they can express SAA3, and this autocrine mediator acts independently of IL-1 alpha to control the low level of collagenase expression that can be stimulated by PMA. These results provide further evidence for a newly emerging paradigm of collagenase regulation which emphasizes the requirement for extracellular routing of signals. They also suggest that SAA3 might be utilized independently of IL-1 alpha to control tissue remodeling in vivo.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Apolipoproteins / physiology*
  • Autocrine Communication
  • Cell Size
  • Cells, Cultured
  • Collagenases / metabolism*
  • Cornea / cytology
  • Feedback
  • Fibroblasts / cytology
  • Fibroblasts / enzymology*
  • Fluorescent Antibody Technique, Indirect
  • Gene Expression Regulation, Enzymologic
  • Interleukin-1 / physiology*
  • RNA, Messenger / genetics
  • Rabbits
  • Serum Amyloid A Protein / physiology*
  • Signal Transduction
  • Tetradecanoylphorbol Acetate / pharmacology


  • Apolipoproteins
  • Interleukin-1
  • RNA, Messenger
  • Serum Amyloid A Protein
  • Collagenases
  • Tetradecanoylphorbol Acetate