Regulation of expression of stromyelysin-1 by proinflammatory cytokines in mouse brain astrocytes

Stromelysin-1 belongs to matrix metalloproteinases responsible for proteolytic degradation of extracellular matrix in many tissues during various diseases, especially those involving inflammation. We studied the induced expression of stromelysin-1 in primary cultures of mouse brain astrocytes stimulated with various cytokines and cellular growth factors. Interleukin-1-beta (IL-1beta), tumor necrosis factor alpha (TNFalpha) and a mixture of IL-1, TNF and epidermal growth factor (EGF) significantly increased the level of stromelysin-1 mRNA in mouse astrocytes while interferon-gamma (IFN-gamma) inhibited this response or was without effect. This accumulation of specific mRNA was preceded by activation of two examined transcription factors: NFkappaB and AP-1. However, experiments with known inhibitors of activation of these transcription factors: pyrrolidine dithiocarbamate (PDTC), parthenolide and curcumin, indicate that NFkappaB and AP-1 cannot be solely responsible for the cytokine induced expression of stromelysin-1 gene in mouse astrocytes.