Human endometase/
matrilysin-2/matrix metalloproteinase-26 (MMP-26) is an
endopeptidase mostly produced by human
carcinoma cells. While
MMPs are thought to regulate the dynamics of extracellular matrix turnover, new evidence shows that these
enzymes may play a critical regulatory role in
inflammation. To investigate the role of MMP-26 in
inflammation, three different variants of
androgen repressed human
prostate cancer (ARCaP) cells were investigated in the study: parental, MMP-26 sense
cDNA-transfected, and MMP-26 antisense
cDNA-transfected ARCaP cells.
Protein lysates and
RNA from control and genetically modified cells were analyzed by Western blotting and real-time reverse transcription polymerase chain reaction on arrays of genes critical to the inflammatory response. In comparison to parental controls, up-regulation of MMP-26 expression in MMP-26 sense
cDNA-transfected cells resulted in a decrease in inflammatory genes expression. Conversely, inflammatory genes were up-regulated in MMP-26 antisense
cDNA-transfected cells. Therefore, modulation of MMP-26 levels significantly affects the expression of inflammatory genes, suggesting an anti-inflammatory role of MMP-26. To determine a possible mechanism of action, further analysis, at both transcript and
protein levels, revealed a dramatic down-regulation of
interleukin-10 receptor B (IL10RB) in MMP-26 antisense
cDNA-transfected cells. The low level of IL10RB was inversely correlated with
matrix metalloproteinase-9 (MMP-9) expression. Collectively, our data suggest that the deficiency of MMP-26 may promote
inflammation via inhibition of IL10RB-mediated signaling. These results propose a novel anti-
inflammation function of MMP-26 and could provide novel molecular insight of therapeutic targeting.