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, primary epithelial cultures (n = 5) of low-grade human prostatic carcinoma. TIMP-1 mRNA levels were normally low in the primary cell lines, but were inducible by interleukin (IL) 10 and 6. Dose and time-course studies indicated that IL-10 was the most potent stimulator of TIMP-1 expression. Cycloheximide blocked the effects of IL-10 in a reversible manner. In situ hybridization assays with TIMP-1 oligonucleotide antisense probes confirmed the northern blot results and indicated that IL-10 preferentially stimulated TIMP-1 mRNA synthesis. We suggest that IL-10, and to a lesser extent IL-6, may normally influence TIMP-1 expression by human prostatic epithelial cells.