Secretory Leukoprotease Inhibitor Augments Hepatocyte Growth Factor Production in Human Lung Fibroblasts

Secretory leukoprotease inhibitor (SLPI), an 11.7-kD nonglycosylated serine protease inhibitor, is produced and released into the fluids of mucosal surfaces including human lung. It comprises two domains with homologous amino acid sequences: the N-terminal domain possessing antibacterial activity, and the C-terminal domain with antiprotease activity. Here we report the positive regulation of hepatocyte growth factor (HGF) production in human lung fibroblasts exerted by SLPI or its C-terminal domain under physiologic concentrations (1 to 10 μ M). This HGF production by SLPI was unaffected by the addition of interleukin (IL)-1 receptor antagonist. In contrast, human skin fibroblasts exerted no SLPI-stimulated increase in HGF production, despite the fact that IL-1 β increased HGF production with an intensity similar to that of human lung fibroblasts. Both the time-course and dose-response studies in human lung fibroblasts revealed that the induction of HGF messenger RNA (mRNA) and protein occurred in paralle...