Abstract
Matrix metalloproteinases (MMPs) are key enzymes in mammalian tissue
remodeling and inflammation. Recently, we postulated that an endogenous
MMP expressed in the lepidopteran model Galleria mellonella during
metamorphosis causes degradation of collagen-IV, which in turn results
in activation of innate immunity. Here, we report that degradation of
collagen-IV by hemocytes is enhanced upon injection of bacterial
lipopolysaccharide (LPS), and that this activity is sensitive to the
MMP-inhibitor GM6001. Therefore, we screened for enzymes behind this
activity and identified the first MMP from Lepidoptera (Gm1-MMP), and
the third from insects. Gm1-MMP shares homology with the first MMP from
Drosophila (Dm1-MMP) known to be essential for tissue remodeling during
metamorphosis. Using quantitative real-time reverse transcriptase
polymerase chain reaction (RT-PCR) analysis, we confirmed up-regulation
of Gm1-MMP expression after pupation, when extracellular matrix
breakdown of larval tissues occurs. In addition, we determined that LPS
challenge induces Gm1-MMP expression in hemocytes, implicating its
participation in collagen-IV degradation upon septic injury. These
results suggest dual roles of Gm1-MMP in innate immunity and
metamorphosis. Interestingly, our phylogenetic analysis elucidates that
Gm1-MMP share highest similarity with human MMP-19 and MMP-28, whose
functions in mammalian wounding and inflammatory response have recently
been demonstrated; hence, the present findings may provide insights
into the evolutionarily conserved features of MMPs. (c) 2007 Elsevier
Ltd. All rights reserved.
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