title: Role of serum amyloid A as an intermediate in the IL-1 and PMA-stimulated signaling pathways regulating expression of rabbit fibroblast collagenase.
abstract: 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.
authors.affiliation: Vision Research Laboratory, New England Medical Center, Boston, Massachusetts 02111, USA.
authors.forename: K J
authors.initials: KJ
authors.lastname: Strissel
authors.forename: M T
authors.initials: MT
authors.lastname: Girard
authors.forename: J A
authors.initials: JA
authors.lastname: West-Mays
authors.forename: W B
authors.initials: WB
authors.lastname: Rinehart
authors.forename: J R
authors.initials: JR
authors.lastname: Cook
authors.forename: C E
authors.initials: CE
authors.lastname: Brinckerhoff
authors.forename: M E
authors.initials: ME
authors.lastname: Fini
mesh_terms: D000818:Animals; D001053:Apolipoproteins / Q000502:physiology*; D019898:Autocrine Communication; D048429:Cell Size; D002478:Cells, Cultured; D017364:Collagenases / Q000378:metabolism*; D003315:Cornea / Q000166:cytology; D005246:Feedback; D005347:Fibroblasts / Q000166:cytology / Q000201:enzymology*; D019084:Fluorescent Antibody Technique, Indirect; D015971:Gene Expression Regulation, Enzymologic; D007375:Interleukin-1 / Q000502:physiology*; D012333:RNA, Messenger / Q000235:genetics; D011817:Rabbits; D000685:Serum Amyloid A Protein / Q000502:physiology*; D015398:Signal Transduction; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
chemical_list: D001053:Apolipoproteins; D007375:Interleukin-1; D012333:RNA, Messenger; D000685:Serum Amyloid A Protein; D017364:Collagenases; D013755:Tetradecanoylphorbol Acetate