Abstract
Previously, our laboratory showed that interleukin-1
β
(IL-1
β
) secreted by lipopolysaccharide-activated monocytes induces promatrilysin expression in the prostate carcinoma cell line, LNCaP. We now demonstrate that IL-1
β
-induced promatrilysin expression is mediated by an indirect mechanism that requires nuclear factor Kappa B (NF
κ
B)-dependent synthesis of IL-6. Inhibition of protein synthesis with cyclohexamide blocked IL-1
β
-mediated induction of matrilysin mRNA suggesting that synthesis of one or more additional factors is required for IL-1
β
-induced promatrilysin protein expression. Blockage of NF
κ
B transactivation activity abrogated IL-1
β
-induced promatrilysin expression to baseline levels suggesting that NF
κ
B transactivation activity is necessary. Inhibition of IL-6 activity attenuated IL-1
β
-induced promatrilysin, but not NF
κ
B transactivation activity indicating that IL-6 acts downstream of NF
κ
B in potentiation of IL-1
β
-mediated promatrilysin expression. Inhibition of protein synthesis with cyclohexamide did not alter IL-6-induced induction of matrilysin mRNA indicating that, contrary to the mechanism by which IL-1
β
regulates promatrilysin expression, IL-6-mediated matrilysin mRNA expression does not require new protein synthesis. Transient transfection with dominant negative STAT3 inhibited IL-1
β
- and IL-6-induced promatrilysin. These data provide evidence that NF
κ
B-mediated IL-6 synthesis is required for IL-1
β
-induced promatrilysin expression, and IL-6 signaling through STAT3 plays a role in IL-1
β
-induced promatrilysin expression.
