Effect of Matrix Metallopeptidase 13 on the Function of Mouse Bone Marrow-derived Dendritic Cells

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Background:Dendritic cells are professional antigen-presenting ceils found in an immature state in epithelia and interstitial space,where they capture antigens such as pathogens or damaged tissue.Matrix metallopeptidase 13 (MMP-13),a member of the collagenase subfamily,is involved in many different cellular processes and is expressed in murine bone marrow-derived dendritic cells (DCs).The function of MMP-13 in DCs is not well understood.Here,we investigated the effect of MMP-13 on DC maturation,apoptosis,and phagocytosis.Methods:Bone marrow-derived dendritic cells were obtained from C57BL/6 mice.One short-interfering RNA specific for MMP-13 was used to transfect DCs.MMP-13-silenced DCs and control DCs were prepared,and apoptosis was measured using real-time polymerase chain reaction and West blotting.MMP-13-silenced DCs and control DCs were analyzed for surface expression of CD80 and CD86 and phagocytosis capability using flow cytometry.Results:Compared to the control DCs,MMP-13-silenced DCs increased expression ofanti-apoptosis-related genes,BAG1 (control group vs.MMP-13-silenced group:4.08 ± 0.60 vs.6.11 ± 0.87,P =0.008),BCL-2 (control group vs.MMP-13-silenced group:7.54 ± 0.76 vs.9.54 ±1.29,P =0.036),and TP73 (control group vs.MMP-13-silenced group:4.33 ± 0.29 vs.5.60 ± 0.32,P =0.001) and decreased apoptosis-related genes,CASP1 (control group vs.MMP-13-silenced group:3.79 ± 0.67 vs.2.54 ± 0.39,P =0.019),LTBR (control group vs.MMP-13-silenced group:9.23 ± 1.25 vs.6.24 ± 1.15,P =0.012),and CASP4 (control group vs.MMP-13-silenced group:2.07 ± 0.56 vs.0.35 ± 0.35,P =0.002).Protein levels confirmed the same expression patt.MMP-13-silenced groups decreased expression of CD86 on DCs;however,there was no statistical difference in CD80 surface expression.Furthermore,MMP-13-silenced groups exhibited weaker phagocytosis capability.Conclusion:These results indicate that MMP-13 inhibition dampens DC maturation,apoptosis,and phagocytosis.
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