The family of
matrix metalloproteinases (
MMPs) comprises
endopeptidases that are capable of degrading all extracellular matrix components. Given these actions, it is conceivable that
MMPs may play a pathogenic role in
inflammatory 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 (tissue inhibitors of
metalloproteinases; TIMPs) are expressed in muscle during acute inflammatory attacks by studying muscle biopsies obtained from patients diagnosed as having
polymyositis, dermatomyositis,
sporadic inclusion body myositis and, for comparison, from cases of various
muscular dystrophies. 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
inclusion body myositis, whereas the level of expression of TIMPs remained unchanged in comparison with controls. Increased
mRNA levels were associated with enhanced
enzyme expression, as determined by immunoblotting,
gelatin zymography and in situ zymography. Immunohistochemically, MMP-1 could be localized around the sarcolemma of diseased muscle fibres and to cells resembling 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 muscle. Our results imply a pathogenic role for specific
MMPs in the genesis of
inflammatory myopathies, and open new strategies for therapeutic intervention.