CYTOKINE (IL-10, IL-6) INDUCTION OF TISSUE INHIBITOR OF METALLOPROTEINASE-1 IN PRIMARY HUMAN PROSTATE TUMOR-CELL LINES

Northern blots and scintillation counting showed that tissue inhibitor of metalloproteinase 1 (TIMP-1) mRNA was expressed by low passage, pr imary epithelial cultures (n = 5) of low-grade human prostatic carcino ma. TIMP-1 mRNA levels were normally low in the primary cell lines, bu t were inducible by interleukin (IL) 10 and 6. Dose and time-course st udies indicated that IL-10 was the most potent stimulator of TIMP-1 ex pression. Cycloheximide blocked the effects of IL-10 in a reversible m anner. In situ hybridization assays with TIMP-1 oligonucleotide antise nse probes confirmed the northern blot results and indicated that IL-1 0 preferentially stimulated TIMP-1 mRNA synthesis. We suggest that IL- 10, and to a lesser extent IL-6, may normally influence TIMP-1 express ion by human prostatic epithelial cells.