Matrilysin is a matrix metalloprotease that is overexpressed in cancer cells of epithelial origin and in normal tissues during events involving matrix remodeling such as the cycling endometrium. We previously observed that inflamed ductule and acinar epithelia in the prostate also overexpress matrilysin. The presence of infiltrating macrophages in these areas prompted us to determine if factors secreted from monocytes could induce matrilysin expression in a human prostatic cell line. Conditioned media collected from the monocyte cell line THP-1 following lipopolysaccharide treatment substantially induced matrilysin protein and mRNA expression in LNCaP prostate carcinoma cells. Matrilysin expression in LNCaP cells was also induced by recombinant interleukin (IL)-1 (50 pM), but not by equimolar concentrations of recombinant tumor necrosis factor-␣ or IL-6. The matrilysin-inducing activity of THP-1 conditioned medium was completely abrogated by preincubation with a neutralizing antibody to IL-1. Transient transfection analyses with a chimeric human matrilysin promoter-chloramphenicol acetyltransferase reporter construct demonstrated that IL-1 activates transcription through the matrilysin promoter in LNCaP cells. This is the first report of matrilysin induction by an inflammatory cytokine in a cell line of epithelial origin, and the results suggest a potential mechanism for the overexpression of matrilysin in inflamed ducts and glands of the prostate.The matrix metalloproteases are a family of enzymes that degrade extracellular matrix proteins. Matrilysin (PUMP-1, MMP-7) is a relatively recently described matrix metalloprotease belonging to the stromelysin enzyme subclass (reviewed in Ref. 1). Matrilysin is capable of degrading a diverse set of extracellular matrix proteins including proteoglycans, fibronectin, entactin, laminin, gelatin, and elastin. The expression of matrilysin has been demonstrated in the cycling endometrium (2); the involuting rat prostate (3) and uterus (4); developing mononuclear phagocytes (5); and cancers of the breast (6), lung and upper respiratory tract (7), skin (8), stomach and colon (9, 10), and prostate (11). A unique feature of matrilysin expression is that it appears to predominate in epithelial cells of glandular tissue, while other matrix metalloproteases, such as stromelysin and the gelatinases, are more commonly expressed by cells in the stromal compartment (1). The expression of matrilysin during normal and pathological events that involve matrix remodeling and the cell type specificity of this expression imply an important role for matrilysin in these events.In the normal prostate, we have observed that inflamed ductule and acinar epithelia frequently express high levels of matrilysin (11,12). It has been clearly demonstrated by in situ hybridization that the overexpression of matrilysin mRNA is confined to the epithelial cells of these structures and is not present in the surrounding stroma or infiltrating leukocytes (12). Immunohistochemical analysis confirmed that the ex...