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.
Stearns
M
M
Medical Colleges of Pennsylvania, Department of Pathology and Molecular Biology, Philadelphia 19129, USA.
Wang
M
M
Stearns
M E
ME
D015152:Blotting, Northern; D004848:Epithelium / Q000378:metabolism; D006023:Glycoproteins / Q000096:biosynthesis* / Q000235:genetics; D006801:Humans; D017403:In Situ Hybridization; D016753:Interleukin-10 / Q000494:pharmacology*; D015850:Interleukin-6 / Q000494:pharmacology*; D008297:Male; D011471:Prostatic Neoplasms / Q000378:metabolism*; D011480:Protease Inhibitors / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D019714:Tissue Inhibitor of Metalloproteinases; D014407:Tumor Cells, Cultured / Q000187:drug effects
D006023:Glycoproteins; D015850:Interleukin-6; D011480:Protease Inhibitors; D012333:RNA, Messenger; D019714:Tissue Inhibitor of Metalloproteinases; D016753:Interleukin-10