Expression of specific matrix metalloproteinases in inflammatory myopathies

The family of matrix metalloproteinases (MMPs) comprises endopeptidases tha t are capable of degrading all extracellular matrix components, Given these actions, it is conceivable that MMPs may play a pathogenic role in inflamm atory myopathies, These immune-mediated disorders are characterized by the invasion of mononuclear phagocytes and T lymphocytes and the loss of muscle fibres, We examined whether specific MMPs and their natural inhibitors (ti ssue inhibitors of metalloproteinases; TIMPs) are expressed in muscle durin g acute inflammatory attacks by studying muscle biopsies obtained from pati ents diagnosed as having polymyositis, dermatomyositis, sporadic inclusion body myositis and, for comparison, from cases of various muscular dystrophi es. Quantitative polymerase chain reaction analysis revealed significantly elevated mRNA expression of interstitial collagenase (MMP-1) and gelatinase B (MMP-9) in polymyositis and dermatomyositis and to a lesser extent in in clusion body myositis, whereas the level of expression of TIMPs remained un changed in comparison with controls, Increased mRNA levels were associated with enhanced enzyme expression, as determined by immunoblotting, gelatin z ymography and in situ zymography, Immunohistochemically, MMP-1 could be loc alized around the sarcolemma of diseased muscle fibres and to cells resembl ing fibroblasts, whereas MMP-9 seemed to be expressed primarily by invading T lymphocytes, Raised levels of MMPs could not be detected in the sera of affected patients, emphasizing the crucial action of MMPs in the inflamed m uscle, Our results imply a pathogenic role for specific MMPs in the genesis of inflammatory myopathies, and open new strategies for therapeutic interv ention.