Inhibition of matrix metalloproteinase‐9 by interferons and TGF‐β1 through distinct signalings accounts for reduced monocyte invasiveness

Abstract
Cytokines may provide signals for regulating human monocyte matrix metalloproteinase‐9 (MMP‐9) activity. In this study, we investigated the roles of interferons (IFN) type I/II and transforming growth factor‐β1 (TGF‐β1) in MMP‐9‐mediated invasiveness. MMP‐9 antibody and inhibitor, IFNs and TGF‐β1 inhibited monocyte transmigration through Matrigel. IFNs and TGF‐β1 downregulated MMP‐9 mRNA, protein and activity levels. The inhibitory action of IFNs was associated with the STAT1/IRF‐1 pathway since the JAK inhibitor AG490 blocked STAT1 phosphorylation, IRF‐1 synthesis and counteracted the blockade of MMP‐9 release. TGF‐β1‐mediated MMP‐9 inhibition appeared STAT1/IRF‐1‐independent but reversed by the protein tyrosine kinase inhibitor tyrphostin 25. Our data point out the importance of IFNs and TGF‐β1 in the control of monocyte MMP‐9‐mediated extravasation.