title: The Anti-inflammatory Role of Endometase/Matrilysin-2 in Human Prostate Cancer Cells.
abstract: 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.
authors.affiliation: 1. Department of Chemistry and Biochemistry, Florida State University, Tallahassee, FL 32306, USA;
authors.forename: Zahraa I
authors.initials: ZI
authors.lastname: Khamis
authors.forename: Diego A R
authors.initials: DA
authors.lastname: Zorio
authors.forename: Leland W K
authors.initials: LW
authors.lastname: Chung
authors.forename: Qing-Xiang Amy
authors.initials: QX
authors.lastname: Sang
keywords: inflammatory genes; interleukin-10 receptor B; matrix metalloproteinase-26; matrix metalloproteinase-9.; real-time reverse transcription polymerase chain reaction