1. Department of Chemistry and Biochemistry, Florida State University, Tallahassee, FL 32306, USA;
2. Institute of Molecular Biophysics, Florida State University, Tallahassee, FL 32306, USA;
3. Department of Medicine, The Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, 8750 Beverly Blvd. Atrium 103, Los Angeles, CA 90048, USA.
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.
Keywords: matrix metalloproteinase-26, inflammatory genes, real-time reverse transcription polymerase chain reaction, interleukin-10 receptor B, matrix metalloproteinase-9.