INTERLEUKIN-1-BETA SECRETED FROM MONOCYTIC CELLS INDUCES THE EXPRESSION OF MATRILYSIN IN THE PROSTATIC CELL-LINE LNCAP

Matrilysin is a matrix metalloprotease that is overexpressed in cancer cells of epithelial origin and in normal tissues during events involv ing matrix remodeling such as the cycling endometrium. We previously o bserved that inflamed ductule and acinar epithelia in the prostate als o overexpress matrilysin. The presence of infiltrating macrophages in these areas prompted us to determine if factors secreted from monocyte s could induce matrilysin expression in a human prostatic cell line, C onditioned 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 exp ression in LNCaP cells was also induced by recombinant interleukin (IL )-1 (50 pM), but not by equimolar concentrations of recombinant tumor necrosis factor-alpha or IL-6. The matrilysin-inducing activity of THP -1 conditioned medium was completely abrogated by preincubation with a neutralizing antibody to IL-1 beta. Transient transfection analyses w ith a chimeric human matrilysin promoter-chloramphenicol acetyltransfe rase reporter construct demonstrated that IL-1 beta activates transcri ption through the matrilysin promoter in LNCaP cells. This is the firs t report of matrilysin induction by an inflammatory cytokine in a cell line of epithelial origin, and the results suggest a potential mechan ism for the overexpression of matrilysin in inflamed ducts and glands of the prostate.