Interleukin-6 and Transforming Growth Factor-β1 Control Expression of Cathepsins B and L in Human Lung Epithelial Cells

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Abstract
Cathepsins B and L are commonly expressed cysteine proteinases that play a major role in lysosomal bulk proteolysis, protein processing, matrix degradation, and tissue remodeling. Cathepsins are also implicated in tumor progression and metastasis, tissue injury, and inflammation. Cells at sites of inflammation often show upregulation and secretion of cathepsins. The regulation of cathepsin expression by inflammatory mediators is not well understood. The aims of this study were to investigate the effect of the cytokines interleukin-1β (IL-1β), IL-6, IL-10, transforming growth factor-β1 (TGF-β1), and hepatocyte growth factor (HGF) on expression of cathepsin B and cathepsin L mRNA (quantitative RT-PCR), on protein expression (ELISA, Western blot), and also on enzymatic activity of cathepsins B and L. Investigations were performed using the human lung epithelial cell line A-549. IL-6 was found to induce a concentration-dependent increase in mRNA expression, protein concentration, and enzymatic activity of cathepsin L. Cathepsin B mRNA and protein expression were not affected by IL-6. In contrast, TGF-β1 decreased the amount of cathepsin L mRNA and cathepsin B mRNA. At protein level, it was shown that TGF-β1 clearly reduced the concentration of cathepsin L but not cathepsin B. The cytokines IL-1β, IL-10, and HGF were found to exert no effect on cathepsin B and L expression. In conclusion, these results are the first to show that IL-6 and TGF-β1 have opposite effects on the regulation of expression of cathepsins B and L in A-549 human lung epithelial cells. The proinflammatory cytokine IL-6 induced an upregulation of cathepsin L, whereas TGF-β1 suppressed cathepsin B and L expression. Further studies are needed to clarify the mechanism that affects cathepsin B and L expression.