Expression profiles of matrix metalloproteinase 9 in teleost fish provide evidence for its active role in initiation and resolution of inflammation

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Abstract
Summary: Matrix metalloproteinase 9 (MMP‐9) belongs to a family of zinc‐dependent endopeptidases. As a consequence of its ability to cleave structural extracellular matrix molecules, mammalian MMP‐9 is associated with vital inflammatory processes such as leucocyte migration and tissue remodelling and regeneration. Interestingly, MMP‐9 genes have been identified in fish, but functional data are still limited and focus on the involvement of MMP‐9 in embryonic development, reproduction and post‐mortem tenderization. Here, we describe the involvement of MMP‐9 in the innate immunity of carp. In carp, MMP‐9 was most notably expressed in classical fish immune organs and in peritoneal and peripheral blood leucocytes, indicating a role of MMP‐9 in immune responses. In our well‐characterized zymosan‐induced peritonitis model for carp, we analysed expression of the MMP‐9 gene and the gelatinolytic levels of both pro‐ and activated forms of MMP‐9. The biphasic profile of MMP‐9 mRNA expression indicated involvement during the initial phase of inflammation and during the later phase of tissue remodelling. Also, in vitro stimulation of carp phagocytes with lipopolysaccharide or concanavalin A increased MMP‐9 gene expression, with a peak at 24 hr. The increase of MMP‐9 mRNA correlated with the peak of MMP‐9 gelatinolytic level in culture supernatants. These results provide evidence for an evolutionarily conserved and relevant role of MMP‐9 in the innate immune response.