Interleukin-6 and transforming growth factor-beta 1 control expression of cathepsins B and L in human lung epithelial cells

Cathepsins B and L are commonly expressed cysteine proteinases that play a major role in lysosomal bulk proteolysis, protein processing, matrix degrad ation, and tissue remodeling. Cathepsins are also implicated in tumor progr ession and metastasis, tissue injury, and inflammation. Cells at sites of i nflammation often show upregulation and secretion of cathepsins, The regula tion of cathepsin expression by inflammatory mediators is not well understo od. The aims of this study were to investigate the effect of the cytokines interleukin-1 beta (IL-1 beta), IL-6, IL-10, transforming growth factor-bet a1 (TGF-beta1), and hepatocyte growth factor (HGF) on expression of catheps in B and cathepsin L mRNA (quantitative RT-PCR), on protein expression (ELI SA, Western blot), and also on enzymatic activity of cathepsins B and L, In vestigations were performed using the human lung epithelial cell line A-549 . IL-6 was found to induce a concentration-dependent increase in mRNA expre ssion, protein concentration, and enzymatic activity of cathepsin L. Cathep sin B mRNA and protein expression were not affected by IL-6. In contrast, T GF-beta1 decreased the amount of cathepsin L mRNA and cathepsin B mRNA. At protein level, it was shown that TGF-beta1 clearly reduced the concentratio n of cathepsin L but not cathepsin B. The cytokines IL-1 beta, IL-10, and H GF were found to exert no effect on cathepsin B and I, expression. In concl usion, these results are the first to show that IL-6 and TGF-beta1 have opp osite effects on the regulation of expression of cathepsins B and L in A-54 9 human lung epithelial cells. The proinflammatory cytokine IL-6 induced an upregulation of cathepsin L, whereas TGF-beta1 suppressed cathepsin B and L expression. Further studies are needed to clarify the mechanism that affe cts cathepsin B and L expression.