Modulation of Keratinocyte-Derived MMP-9 by IL-13: A Possible Role for the Pathogenesis of Epidermal Inflammation

Skin inflammation and remodeling are important pathophysiological features of chronic eczematous skin diseases. Matrix metalloproteinases (MMP) have been described to influence tissue remodeling and to facilitate cell migration through their ability to proteolyse the extracellular matrix. The aim of this study was to investigate the influence of IL-13 on the modulation of MMPs in human primary keratinocytes (KCs). IL-13 stimulation of KCs induced the expression of MMP-9 but not of MMP-3 or MMP-2 at mRNA level. A major substrate of MMP-9 is the type IV collagen of the basement membrane. IL-13 induced the release of active MMP-9 in KCs as detected by an ELISA-based assay. Moreover, migration of lymphocytes cultured with IL-13-activated KC showed increased migration through a basement membrane equivalent. The MMP-9 expression was prominent near the basement membrane of IL-13-treated skin biopsies. Collagen type IV staining pointed to a loss of this major basement membrane constituent in IL-13-treated skin. Finally, we demonstrated the concomitant mRNA expression of MMP-9 and IL-13 in biopsies from lesional, acutely inflamed eczematous skin. Our results suggest that release of active MMP-9 by IL-13-stimulated KCs may play a crucial role in skin inflammation by facilitating migration of leukocytes into the epidermis.