Interleukin-1β-induced promatrilysin expression is mediated by NFκB-regulated synthesis of interleukin-6 in the prostate carcinoma cell line, LNCaP

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